Page last updated: 2024-10-15

rifapentine

Description

rifapentine: cyclopentyl derivative of rifampicin [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID135403821
CHEMBL ID1660
CHEBI ID45304
SCHEMBL ID41590
MeSH IDM0069928

Synonyms (76)

Synonym
3-(4-cyclopentyl-1-piperazinyl)iminomethylrifamycin sv
rifapentinum [latin]
rifapentina [spanish]
antibiotic dl 473it
3-(((4-cyclopentyl-1-piperazinyl)imino)methyl)rifamycin sv
r-773
rifamycin, 3-(((4-cyclopentyl-1-piperazinyl)imino)methyl)-
einecs 262-743-9
3-(n-(4-cyclopentyl-1-piperazinyl)formimidoyl)rifamycin
drg-0283
R773 ,
AB01209744-03
m000473 ,
dl-473 ,
rifapentin
mdl-473
mdl473
rifamycin af/acpp
ktc 1
cyclopentyl rifampin
priftin
dl 473
r 77-3
rpe
dl473
3-[n-(4-cyclopentyl-1-piperazinyl)formimidoyl]rifamycin
[[(e)-(4-cyclopentylpiperazin-1-yl)iminomethyl]-pentahydroxy-methoxy-heptamethyl-dioxo-[?]yl] acetate
mdl 473
61379-65-5
C08059
rifapentine
3-(((4-cyclopentyl-1-piperazinyl)imino)methyl)rifamycin
cyclopentylrifampicin
(7s,9e,11s,12r,13s,14r,15r,16r,17s,18s,19e,21z)-26-{(e)-[(4-cyclopentylpiperazin-1-yl)imino]methyl}-2,15,17,27,29-pentahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-6,23-dioxo-8,30-dioxa-24-azatetracyclo[23.3.1.1(4,7).0(5,28)]triaconta-1(28),1(29),2,4
CHEBI:45304 ,
DB01201
D00879
priftin (tn)
rifapentine (usan/inn)
(2s,12z,14e,16s,17s,18r,19r,20r,21s,22r,23s,24e)-8-{(e)-[(4-cyclopentylpiperazin-1-yl)imino]methyl}-5,6,9,17,19-pentahydroxy-23-methoxy-2,4,12,16,18,20,22-heptamethyl-1,11-dioxo-1,2-dihydro-2,7-(epoxypentadeca[1,11,13]trienoimino)naphtho[2,1-b]furan-21-yl
ktc-1
antibiotic dl-473it
r-77-3
CHEMBL1660
prifitin
dtxsid8041115 ,
dtxcid6021115
rifapentinum
rifapentina
unii-xjm390a33u
xjm390a33u ,
rifapentine [usan:inn:ban]
3-((4-cyclopentyl-1-piperazinyl)imino)methyl)rifamycin
rifapentine [who-dd]
rifapentine [vandf]
rifapentine [inn]
rifapentine [usan]
rifapentine [mart.]
rifapentine [orange book]
rifapentine [mi]
CCG-220467
AB01209744-01
SCHEMBL41590
KS-1409
AKOS024255723
rifapentine, antibiotic for culture media use only
W-105162
AB01209744_04
HMS3713M16
bdbm50248298
[(7s,9e,11s,12r,13s,14r,15r,16r,17s,18s,19e,21z)-26-[(e)-(4-cyclopentylpiperazin-1-yl)iminomethyl]-2,15,17,27,29-pentahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-6,23-dioxo-8,30-dioxa-24-azatetracyclo[23.3.1.14,7.05,28]triaconta-1(29),2,4,9,19,21,25
dl 473;cyclopentylrifampicin
mfcd00866806
(7s,9e,11s,12r,13s,14r,15r,16r,17s,18s,19e,21z)-26-((e)-((4-cyclopentylpiperazin-1-yl)imino)methyl)-2,15,17,27,29-pentahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-6,23-dioxo-8,30-dioxa-24-azatetracyclo(23.3.1.1(4,7).0(5,28))triaconta-1(28),1(29),2,4
rifapentine (mart.)
rifapentinum (latin)

Research Excerpts

Overview

Rifapentine is a rifamycin derivate approved by the US Food and Drug Administration in 1998 for the treatment of active, drug-susceptible tuberculosis (TB) Rifapetine is currently in phase III trials.

ExcerptReference
"Rifapentine is a rifamycin with unique bactericidal activity against Mycobacterium tuberculosis. "( Decreased serum voriconazole levels caused by hepatic enzyme induction after rifapentine discontinuation: a case report and literature review.
Cai, XJ; Jing, YP; Li, JM; Ling, GM; Zhang, RY, 2023
)
"Rifapentine is a potent inducer of hepatic microsomal enzymes. "( Decreased serum voriconazole levels caused by hepatic enzyme induction after rifapentine discontinuation: a case report and literature review.
Cai, XJ; Jing, YP; Li, JM; Ling, GM; Zhang, RY, 2023
)
"Rifapentine is a rifamycin derivate approved by the US Food and Drug Administration in 1998 for the treatment of active, drug-susceptible tuberculosis (TB). "( Clinical and pharmacological hallmarks of rifapentine's use in diabetes patients with active and latent tuberculosis: do we know enough?
Gao, F; Hu, M; Hu, X; Zhao, L; Zheng, C, 2017
)
"Rifapentine is a rifamycin used to treat tuberculosis. "( A Population Pharmacokinetic Analysis Shows that Arylacetamide Deacetylase (AADAC) Gene Polymorphism and HIV Infection Affect the Exposure of Rifapentine.
Charalambous, S; Dawson, R; Denti, P; Dorman, S; Egan, D; Francis, J; Gupte, N; Harrison, TS; Hatherill, M; Jindani, A; McIlleron, HM; Mungofa, S; Olagunju, A; Owen, A; Wiesner, L; Zvada, SP, 2019
)
"Rifapentine is a promising active pharmaceutical ingredient with potential to accelerate treatment of TB if delivered by inhaled administration. "( An update on the use of rifapentine for tuberculosis therapy.
Bai, X; Chan, JG; Traini, D, 2014
)
"Rifapentine is a potent antituberculosis drug currently in phase III trials. "( Novel dosing strategies increase exposures of the potent antituberculosis drug rifapentine but are poorly tolerated in healthy volunteers.
Benson, CA; Cramer, Y; Dooley, KE; Dorman, SE; Haas, DW; Hafner, R; Hogg, E; Hovind, L; Janik, J; Marzinke, MA; Park, JG; Patterson, K; Savic, RM, 2015
)
"Rifapentine (RPT) is a rifamycin antimycobacterial and, as part of a combination therapy, is indicated for the treatment of pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis Although the results from a number of studies indicate that rifapentine has the potential to shorten treatment duration and enhance completion rates compared to other rifamycin agents utilized in antituberculosis drug regimens (i.e., regimens 1 to 4), its optimal dose and exposure in humans are unknown. "( Physiologically Based Pharmacokinetic Model of Rifapentine and 25-Desacetyl Rifapentine Disposition in Humans.
Eppers, GJ; Reisfeld, B; Zurlinden, TJ, 2016
)
"Rifapentine is an anti-tuberculosis (anti-TB) drug with a prolonged half-life, but oral delivery results in low concentrations in the lungs because of its high binding (98%) to plasma proteins. "( Inhalation of Respirable Crystalline Rifapentine Particles Induces Pulmonary Inflammation.
Ashhurst, AS; Britton, WJ; Chan, HK; Nagalingam, G; Parumasivam, T, 2017
)
"Rifapentine is a highly active antituberculosis antibiotic with treatment-shortening potential; however, exposure-response relations and the dose needed for maximal bactericidal activity have not been established. "( Defining the optimal dose of rifapentine for pulmonary tuberculosis: Exposure-response relations from two phase II clinical trials.
Dooley, KE; Dorman, SE; Engle, M; Johnson, JL; MacKenzie, WR; Nahid, P; Nguyen, NV; Nsubuga, P; Peloquin, CA; Savic, RM; Weiner, M; Whitworth, WC, 2017
)
"Rifapentine (RP T) is an antituberculosis drug that may shorten treatment duration when substituted for rifampin (RI F).The maximal tolerated daily dose of RP T and its potential for cytochrome 3A4 induction and autoinduction at clinically relevant doses are unknown. "( Safety and pharmacokinetics of escalating daily doses of the antituberculosis drug rifapentine in healthy volunteers.
Bliven-Sizemore, EE; Burman, WJ; Dooley, KE; Dorman, SE; Fuchs, EJ; Hubbard, WC; Lu, Y; Melia, MT; Nuermberger, EL; Weiner, M, 2012
)
"Rifapentine is a rifamycin antibiotic approved for the treatment of pulmonary infections caused by Mycobacterium tuberculosis. "( Pharmacokinetics of rifapentine in children.
Abdel-Rahman, SM; Blake, MJ; Jacobs, RF; Kearns, GL; Lowery, NK; Sterling, TR, 2006
)
"Rifapentine is a recently approved antituberculosis drug that has not yet been widely used in clinical settings. "( Rifapentine for the treatment of pulmonary tuberculosis.
Ahuja, SD; Kambili, C; Munsiff, SS, 2006
)
"Rifapentine is a long-lived rifamycin derivative currently recommended only in once-weekly continuation-phase regimens."( Daily dosing of rifapentine cures tuberculosis in three months or less in the murine model.
Bishai, WR; Chaisson, RE; Grosset, JH; Nuermberger, EL; Peloquin, CA; Rosenthal, IM; Tyagi, S; Vernon, AA; Williams, KN; Zhang, M, 2007
)
"Rifapentine is a cyclopentyl derivative of rifampin under development for the treatment of Mycobacterium tuberculosis and Mycobacterium avium complex infections. "( Disposition and metabolism of rifapentine, a rifamycin antibiotic, in mice, rats, and monkeys.
Emary, WB; Huh, K; Mathews, B; Toren, PC, 1998
)
"Rifapentine is a long-acting cyclopentyl-derivative of rifampin. "( Disposition and metabolism of 14C-rifapentine in healthy volunteers.
Cheng, L; Eller, MG; Keung, A; Reith, K; Toren, PC; Weir, SJ, 1998
)
"Rifapentine is a rifamycin antibiotic with antimycobacterial activity. "( Rifapentine.
Jarvis, B; Lamb, HM, 1998
)
"Rifapentine is a potent inducer of CYP3A activity. "( Enzyme induction observed in healthy volunteers after repeated administration of rifapentine and its lack of effect on steady-state rifapentine pharmacokinetics: part I.
Cheng, L; Eller, MG; Keung, A; McKenzie, KA; Reith, K; Weir, SJ, 1999
)
"Rifapentine is a cyclopentyl-substituted rifamycin whose serum half-life is five times that of rifampin. "( Acquired rifamycin monoresistance in patients with HIV-related tuberculosis treated with once-weekly rifapentine and isoniazid. Tuberculosis Trials Consortium.
Benator, D; Bozeman, L; Burman, W; Khan, A; Vernon, A, 1999
)
"Rifapentine is a long-acting rifamycin which may be useful for intermittent drug therapy against tuberculosis. "( Analysis of rifapentine for preventive therapy in the Cornell mouse model of latent tuberculosis.
Bishai, WR; Chaisson, RE; Miyazaki, E, 1999
)
"Rifapentine (R773, DL473) is a long-acting antituberculous drug used in China. "( Inductive effects of rifapentine on mice hepatic mixed function oxidase system.
Liu, DY; Wang, YS, 1990
)

Effects

Rifapentine has a long half-life in serum, which suggests a possible treatment once a week for tuberculosis.

ExcerptReference
"Rifapentine has a long half-life in serum, which suggests a possible treatment once a week for tuberculosis. "( Rifapentine and isoniazid once a week versus rifampicin and isoniazid twice a week for treatment of drug-susceptible pulmonary tuberculosis in HIV-negative patients: a randomised clinical trial.
Benator, D; Bhattacharya, M; Bozeman, L; Burman, W; Cantazaro, A; Chaisson, R; Gordin, F; Horsburgh, CR; Horton, J; Khan, A; Lahart, C; Metchock, B; Pachucki, C; Stanton, L; Vernon, A; Villarino, ME; Wang, YC; Weiner, M; Weis, S, 2002
)
"Rifapentine has a long half-life, and has the potential to lengthen intermittent treatment for tuberculosis."( Researchers find new drugs to fight MAC.
, 1995
)

Treatment

ExcerptReference
"All rifapentine-treated mice were lung culture-negative at 3 months but 13% of BALB/c that received cortisone and 73% of nude mice relapsed. "( Treatment of tuberculosis with rifamycin-containing regimens in immune-deficient mice.
Ahmad, Z; Almeida, DV; Converse, PJ; Grosset, JH; Li, SY; Nuermberger, EL; Peloquin, CA; Rosenthal, IM; Zhang, M, 2011
)

Toxicity

A 3-month regimen of weekly isoniazid and rifapentine (3HP) is safe and effective for tuberculosis prevention in adults and children, including those with HIV. 3HP has not been evaluated in pregnancy.

ExcerptReference
"3%] in the RPT 450 mg, RPT 600 mg and RMP groups), as were ⩾grade 3 adverse events (0/54 [0%], 1/51 [2."( Two-stage activity-safety study of daily rifapentine during intensive phase treatment of pulmonary tuberculosis.
Barnes, GL; Carman, D; Chaisson, RE; Dawson, R; Dorman, SE; Efron, A; Gupte, N; Hoffman, J; McIlleron, H; Narunsky, K; Whitelaw, A, 2015
)
" Daily RPT was safe and well-tolerated."( Two-stage activity-safety study of daily rifapentine during intensive phase treatment of pulmonary tuberculosis.
Barnes, GL; Carman, D; Chaisson, RE; Dawson, R; Dorman, SE; Efron, A; Gupte, N; Hoffman, J; McIlleron, H; Narunsky, K; Whitelaw, A, 2015
)
" Eighty children with TBI received a 12-dose once-weekly isoniazid/rifapentine regimen; 79 (99%) completed therapy, 94% reported no adverse events, 1 child had mildly elevated transaminases but 1 adolescent later developed pulmonary TB."( Safety and Adherence for 12 Weekly Doses of Isoniazid and Rifapentine for Pediatric Tuberculosis Infection.
Cruz, AT; Starke, JR, 2016
)
"The traditional treatment of tuberculosis (TB) infection (9 months of daily isoniazid [9H]) is safe but completion rates of <50% are reported."( Completion Rate and Safety of Tuberculosis Infection Treatment With Shorter Regimens.
Cruz, AT; Starke, JR, 2018
)
" We compared the frequency of completion and adverse events (AEs) in children receiving 3HP, 4R, and 9H; the latter 2 regimens could be administered by families (termed self-administered therapy [SAT]) or as directly observed preventive therapy (DOPT); 3HP was always administered under DOPT."( Completion Rate and Safety of Tuberculosis Infection Treatment With Shorter Regimens.
Cruz, AT; Starke, JR, 2018
)
" We aimed to determine whether the INH/RPT-3 regimen had similar or lesser rates of adverse events compared to other LTBI regimens, namely INH for 9 months, INH for 6 months, rifampin for 3 to 4 months, and rifampin plus INH for 3 to 4 months."( A systematic review of adverse events of rifapentine and isoniazid compared to other treatments for latent tuberculosis infection.
Alvarez, GG; Barbeau, P; Hamel, C; Hutton, B; Pease, C; Skidmore, B; Wolfe, D; Yazdi, F, 2018
)
"gov, and Canadian Agency for Drugs and Technologies in Health's Gray Matters Light for randomized, postmarketing, and comparative nonrandomized studies of patients with confirmed LTBI that reported the frequency of at least 1 adverse event of relevance for a regimen of interest."( A systematic review of adverse events of rifapentine and isoniazid compared to other treatments for latent tuberculosis infection.
Alvarez, GG; Barbeau, P; Hamel, C; Hutton, B; Pease, C; Skidmore, B; Wolfe, D; Yazdi, F, 2018
)
" Although inconsistent event reporting and high heterogeneity limited comparisons, the adverse event profile of INH/RPT-3 appeared generally favorable."( A systematic review of adverse events of rifapentine and isoniazid compared to other treatments for latent tuberculosis infection.
Alvarez, GG; Barbeau, P; Hamel, C; Hutton, B; Pease, C; Skidmore, B; Wolfe, D; Yazdi, F, 2018
)
"While INH/RPT-3 had an overall low frequency of adverse events compared to INH monotherapy, reporting of adverse events for many regimens was limited meaning results should be interpreted cautiously."( A systematic review of adverse events of rifapentine and isoniazid compared to other treatments for latent tuberculosis infection.
Alvarez, GG; Barbeau, P; Hamel, C; Hutton, B; Pease, C; Skidmore, B; Wolfe, D; Yazdi, F, 2018
)
" Incidents of systemic adverse reactions (SARs) and treatment interruption rates in an elderly group (≥60 years old) and a young group (<60 years old) were analyzed."( Safety and treatment completion of latent tuberculosis infection treatment in the elderly population-A prospective observational study in Taiwan.
Chen, CY; Feng, JY; Huang, WC; Lee, SS; Li, CP; Lin, CB; Lin, SM; Pan, SW; Shu, CC; Su, WJ; Tung, CL; Wang, TY; Wei, YF, 2020
)
" Owing to an unexpected high frequency of adverse events (70."( Efficacy and safety of weekly rifapentine and isoniazid for tuberculosis prevention in Chinese silicosis patients: a randomized controlled trial.
Cai, LM; Hong, JJ; Huang, XT; Jiang, T; Lin, MY; Ling, Q; Liu, XF; Ma, CL; Mao, JC; Pan, KC; Peng, GQ; Ruan, QL; Shao, LY; Shen, YJ; Wang, XD; Wang, XZ; Wu, J; Wu, TZ; Yang, QL; Zhang, WH, 2021
)
" The regimen must be used with caution because of the high rates of adverse effects."( Efficacy and safety of weekly rifapentine and isoniazid for tuberculosis prevention in Chinese silicosis patients: a randomized controlled trial.
Cai, LM; Hong, JJ; Huang, XT; Jiang, T; Lin, MY; Ling, Q; Liu, XF; Ma, CL; Mao, JC; Pan, KC; Peng, GQ; Ruan, QL; Shao, LY; Shen, YJ; Wang, XD; Wang, XZ; Wu, J; Wu, TZ; Yang, QL; Zhang, WH, 2021
)
" No other adverse events were observed."( Safety and feasibility of 1 month of daily rifapentine plus isoniazid to prevent tuberculosis in children and adolescents: a prospective cohort study.
Amanullah, F; Becerra, MC; Fareed, U; Farooq, S; Hussain, H; Jaswal, M; Keshavjee, S; Khan, AJ; Khan, H; Malik, AA; Nasir, K; Safdar, N; Shahbaz, S, 2021
)
"Effective yet safe treatment of latent tuberculosis is important for preventing the spread of tuberculosis and the progression to active disease in pediatric patients."( Adverse events associated with weekly short course isoniazid and rifapentine therapy in pediatric patients with latent tuberculosis: A chart and literature review.
Boyce, C; Huang, FS; Khalil, N; Kohlrieser, CM; Peck, GM; Schlaudecker, EP; Staat, MA, 2021
)
"In this retrospective chart review, pediatric patients ages 2-20 years receiving 3HP with DOT for latent tuberculosis experienced frequent adverse events, more severe adverse events such as anaphylaxis, and higher treatment discontinuation than that which has been previously reported in the literature."( Adverse events associated with weekly short course isoniazid and rifapentine therapy in pediatric patients with latent tuberculosis: A chart and literature review.
Boyce, C; Huang, FS; Khalil, N; Kohlrieser, CM; Peck, GM; Schlaudecker, EP; Staat, MA, 2021
)
"Our data suggests that the short course combination regimen for pediatric latent tuberculosis patients may have a higher adverse event rate than previously established."( Adverse events associated with weekly short course isoniazid and rifapentine therapy in pediatric patients with latent tuberculosis: A chart and literature review.
Boyce, C; Huang, FS; Khalil, N; Kohlrieser, CM; Peck, GM; Schlaudecker, EP; Staat, MA, 2021
)
" A 3-month regimen of weekly isoniazid and rifapentine (3HP) is safe and effective for tuberculosis prevention in adults and children, including those with HIV, but 3HP has not been evaluated in pregnancy."( Pharmacokinetics and Safety of 3 Months of Weekly Rifapentine and Isoniazid for Tuberculosis Prevention in Pregnant Women.
Bradford, S; Britto, P; Chakhtoura, N; Chalermchockcharoentkit, A; Chipato, T; Dooley, KE; Gupta, A; Jayachandran, P; Kamthunzi, P; Langat, D; Mathad, JS; Montepiedra, G; Norman, J; Patil, S; Popson, S; Rouzier, V; Savic, R; Townley, E; Wiesner, L; Zhang, N, 2022
)
" There were no drug-related serious adverse events, treatment discontinuations, or tuberculosis cases in women or infants."( Pharmacokinetics and Safety of 3 Months of Weekly Rifapentine and Isoniazid for Tuberculosis Prevention in Pregnant Women.
Bradford, S; Britto, P; Chakhtoura, N; Chalermchockcharoentkit, A; Chipato, T; Dooley, KE; Gupta, A; Jayachandran, P; Kamthunzi, P; Langat, D; Mathad, JS; Montepiedra, G; Norman, J; Patil, S; Popson, S; Rouzier, V; Savic, R; Townley, E; Wiesner, L; Zhang, N, 2022
)
" Eligible studies compared 3HP or 4R to 6 months or 9 months of isoniazid and reported treatment completion, adverse events, or incidence of tuberculosis disease."( Completion, safety, and efficacy of tuberculosis preventive treatment regimens containing rifampicin or rifapentine: an individual patient data network meta-analysis.
Belknap, R; Benedetti, A; Borisov, A; Campbell, JR; Chaisson, RE; Chan, PC; Martinson, N; Menzies, D; Nahid, P; Scott, NA; Sizemore, E; Sterling, TR; Villarino, ME; Wang, JY; Winters, N, 2023
)
" For treatment-related adverse events leading to drug discontinuation, risks were higher for 3HP than for 4R for adverse events of any severity (aRR 2·86 [2·12-4·21]; aRD 0·03 [0·02-0·05]) and for grade 3-4 adverse events (aRR 3·46 [2·09-6·17]; aRD 0·02 [0·01-0·03])."( Completion, safety, and efficacy of tuberculosis preventive treatment regimens containing rifampicin or rifapentine: an individual patient data network meta-analysis.
Belknap, R; Benedetti, A; Borisov, A; Campbell, JR; Chaisson, RE; Chan, PC; Martinson, N; Menzies, D; Nahid, P; Scott, NA; Sizemore, E; Sterling, TR; Villarino, ME; Wang, JY; Winters, N, 2023
)
"In the absence of RCTs, our individual patient data network meta-analysis indicates that 3HP provided an increase in treatment completion over 4R, but was associated with a higher risk of adverse events."( Completion, safety, and efficacy of tuberculosis preventive treatment regimens containing rifampicin or rifapentine: an individual patient data network meta-analysis.
Belknap, R; Benedetti, A; Borisov, A; Campbell, JR; Chaisson, RE; Chan, PC; Martinson, N; Menzies, D; Nahid, P; Scott, NA; Sizemore, E; Sterling, TR; Villarino, ME; Wang, JY; Winters, N, 2023
)
" Of the 3 withdrawals, 2 were attributed to drug-related adverse events."( Pharmacokinetics, Safety, and Tolerability of Once-Daily Darunavir With Cobicistat and Weekly Isoniazid/Rifapentine.
Adeojo, L; Brooks, KM; Bunn, HT; George, JM; Kovacs, JA; Kumar, P; Pau, AK; Peloquin, CA; Swaim, D, 2023
)

Pharmacokinetics

Study was undertaken to characterize the pharmacokinetic profiles of rifapentine and its active metabolite, 25-desacetlyl rifAPentine, in elderly men. Maximum plasma concentration was lower, time to maximum plasma concentration (tmax) was greater, and elimination half-life was longer in the patients with moderate-to-severe hepatic dysfunction.

ExcerptReference
" Terminal plasma half-life ranged between 14 and 18 hours; the compound is eliminated mainly via the bile with the feces (92% of dose)."( Pharmacokinetics of rifapentine, a new long lasting rifamycin, in the rat, the mouse and the rabbit.
Assandri, A; Cristina, T; Ratti, B, 1984
)
" Maximum plasma concentration of rifapentine was lower, time to maximum plasma concentration (tmax) was greater, and elimination half-life (t 1/2) was longer in the patients with moderate-to-severe hepatic dysfunction than in those with mild-to-moderate dysfunction."( Pharmacokinetics of rifapentine in patients with varying degrees of hepatic dysfunction.
Eller, MG; Keung, AC; Weir, SJ, 1998
)
"This study was undertaken to characterize the pharmacokinetic profiles of rifapentine and its active metabolite, 25-desacetlyl rifapentine, in elderly men."( Single-dose pharmacokinetics of rifapentine in elderly men.
Eller, MG; Keung, AC; Weir, SJ, 1998
)
" The control group consisted of 20 healthy, young (18-45 years) males volunteers from a previous, single-dose (600 mg) rifapentine pharmacokinetic study."( Single-dose pharmacokinetics of rifapentine in elderly men.
Eller, MG; Keung, AC; Weir, SJ, 1998
)
" Disposition of rifapentine was monophasic with a mean terminal half-life of 19."( Single-dose pharmacokinetics of rifapentine in elderly men.
Eller, MG; Keung, AC; Weir, SJ, 1998
)
"Because the aged-related changes in the pharmacokinetic profile of rifapentine observed in this study were modest and unlikely to be associated with toxicity, no dosage adjustments for this antibiotic are recommended in elderly patients."( Single-dose pharmacokinetics of rifapentine in elderly men.
Eller, MG; Keung, AC; Weir, SJ, 1998
)
" Plasma samples were obtained at frequent intervals for up to 72 hr after the dose to determine the pharmacokinetic (PK) parameters of rifapentine and its active metabolite, 25-desacetyl-rifapentine."( Single-dose pharmacokinetics of rifapentine in women.
Eller, MG; Keung, AC; Weir, SJ, 1998
)
" Pharmacokinetic data from a previously published healthy volunteer study were used for comparison."( Pharmacokinetics of rifapentine in subjects seropositive for the human immunodeficiency virus: a phase I study.
Eller, MG; Keung, AC; Nicolau, DP; Nightingale, CH; Owens, RC; Weir, SJ, 1999
)
" Subsequently model-independent methods were used to determine the pharmacokinetic profiles for each subject."( Rifapentine pharmacokinetics in adolescents.
Abdel-Rahman, S; Johnson, K; Kauffman, RE; Kearns, GL; Marshall, JD, 1999
)
" These data provide a pharmacokinetic rationale for extended-interval dosing."( Single-dose intrapulmonary pharmacokinetics of rifapentine in normal subjects.
Conte, JE; Golden, JA; Kipps, J; Lin, ET; McQuitty, M; Zurlinden, E, 2000
)
" The present pharmacokinetic study supports further trials to determine the optimal rifapentine dose for treatment of tuberculosis."( Pharmacokinetics of rifapentine at 600, 900, and 1,200 mg during once-weekly tuberculosis therapy.
Bock, N; Burman, WJ; Goldberg, S; Hayden, K; Khan, A; Peloquin, CA; Sterling, TR; Vernon, A; Weiner, M; Weis, S; Zhao, Z, 2004
)
" Special reference was made to studying the influence of previous exposure to rifampin (RIF) and the variability in pharmacokinetic parameters between patients and between occasions and the influence of different covariates."( Population pharmacokinetics of rifapentine and its primary desacetyl metabolite in South African tuberculosis patients.
Langdon, G; McFadyen, L; McIlleron, H; Simonsson, US; Smith, P; Wilkins, J, 2005
)
" Pharmacokinetic parameters were determined using a model-independent approach."( Pharmacokinetics of rifapentine in children.
Abdel-Rahman, SM; Blake, MJ; Jacobs, RF; Kearns, GL; Lowery, NK; Sterling, TR, 2006
)
" Pharmacokinetic data were analyzed by nonlinear mixed-effect modeling using NONMEM."( Effects of four different meal types on the population pharmacokinetics of single-dose rifapentine in healthy male volunteers.
Fourie, PB; McIlleron, HM; Mitchison, D; Roscigno, G; Simonsson, US; Smith, PJ; Van Der Walt, JS; Zvada, SP, 2010
)
" In order to gain insight into these discrepant findings, we conducted a steady-state pharmacokinetic (PK) study in healthy guinea pigs to study the metabolism and autoinduction of RIF and RFP."( Preliminary pharmacokinetic study of repeated doses of rifampin and rifapentine in guinea pigs.
Alsultan, A; Dutta, NK; Karakousis, PC; Peloquin, CA, 2013
)
" We evaluated the effect of rifapentine on the pharmacokinetic properties of raltegravir."( Pharmacokinetic interaction of rifapentine and raltegravir in healthy volunteers.
Egelund, EF; Engle, M; Gelfond, JA; Kiser, M; Mac Kenzie, W; Peloquin, CA; Prihoda, TJ; Weiner, M, 2014
)
"In 16 subjects who completed the study, coadministration of raltegravir with rifapentine (900 mg once weekly; Period 2) compared with raltegravir alone resulted in the geometric mean of the raltegravir AUC from 0 to 12 h (AUC0-12) being increased by 71%; the peak concentration increased by 89% and the trough concentration decreased by 12%."( Pharmacokinetic interaction of rifapentine and raltegravir in healthy volunteers.
Egelund, EF; Engle, M; Gelfond, JA; Kiser, M; Mac Kenzie, W; Peloquin, CA; Prihoda, TJ; Weiner, M, 2014
)
" The pharmacokinetic profiles of bedaquiline and M2 were compared over 336 h after the administration of bedaquiline alone and in combination with steady-state rifapentine or rifampin."( Evaluation of the pharmacokinetic interaction between repeated doses of rifapentine or rifampin and a single dose of bedaquiline in healthy adult subjects.
Egizi, E; Erondu, N; Ginsberg, A; Murray, S; Pauli, E; Rouse, DJ; Severynse-Stevens, D; Winter, H, 2015
)
"Participants receiving daily rifapentine and isoniazid with efavirenz had pharmacokinetic evaluations at baseline and weeks 2 and 4 of concomitant therapy."( Efavirenz Pharmacokinetics and Pharmacodynamics in HIV-Infected Persons Receiving Rifapentine and Isoniazid for Tuberculosis Prevention.
Andersen, JW; Bao, Y; Benson, CA; Chaisson, RE; Fletcher, CV; Gupta, A; Kim, P; Mohapi, L; Mwelase, T; Podany, AT; Supparatpinyo, K; Swindells, S, 2015
)
" To help inform such an optimization, a physiologically based pharmacokinetic (PBPK) model was developed to predict time course, tissue-specific concentrations of RPT and its active metabolite, 25-desacetyl rifapentine (dRPT), in humans after specified administration schedules for RPT."( Physiologically Based Pharmacokinetic Model of Rifapentine and 25-Desacetyl Rifapentine Disposition in Humans.
Eppers, GJ; Reisfeld, B; Zurlinden, TJ, 2016
)
" While concomitant food intake and HIV infection explain part of the pharmacokinetic variability associated with rifapentine, few studies have evaluated the contribution of genetic polymorphisms."( A Population Pharmacokinetic Analysis Shows that Arylacetamide Deacetylase (AADAC) Gene Polymorphism and HIV Infection Affect the Exposure of Rifapentine.
Charalambous, S; Dawson, R; Denti, P; Dorman, S; Egan, D; Francis, J; Gupte, N; Harrison, TS; Hatherill, M; Jindani, A; McIlleron, HM; Mungofa, S; Olagunju, A; Owen, A; Wiesner, L; Zvada, SP, 2019
)
" Participants provided sparse pharmacokinetic (PK) sampling at baseline and weeks 2 and 4 for trough nevirapine determination."( Nevirapine pharmacokinetics in HIV-infected persons receiving rifapentine and isoniazid for TB prevention.
Benson, CA; Chaisson, RE; Fletcher, CV; Gupta, A; Hakim, J; Kanyama, C; Langat, D; Leon-Cruz, J; Mwelase, N; Omoz-Oarhe, A; Podany, AT; Supparatpinyo, K; Swindells, S, 2021
)
" Pharmacokinetic sampling was performed with the first (second/third trimester) and twelfth (third trimester/postpartum) doses."( Pharmacokinetics and Safety of 3 Months of Weekly Rifapentine and Isoniazid for Tuberculosis Prevention in Pregnant Women.
Bradford, S; Britto, P; Chakhtoura, N; Chalermchockcharoentkit, A; Chipato, T; Dooley, KE; Gupta, A; Jayachandran, P; Kamthunzi, P; Langat, D; Mathad, JS; Montepiedra, G; Norman, J; Patil, S; Popson, S; Rouzier, V; Savic, R; Townley, E; Wiesner, L; Zhang, N, 2022
)
"A population pharmacokinetic (PPK) study of the correlation of adverse drug reactions (ADRs) with the 3HP regimen (weekly high-dose rifapentine plus isoniazid for 12 doses) for latent tuberculosis infection (LTBI) remains lacking."( Isoniazid level and flu-like symptoms during rifapentine-based tuberculosis preventive therapy: A population pharmacokinetic analysis.
Fujita, Y; Huang, HL; Ieiri, I; Lee, CH; Lee, MC; Muraki, S; Wang, JY, 2023
)

Compound-Compound Interactions

ExcerptReference
"The activity of TLC G-65 (a liposomal gentamicin preparation), alone and in combination with rifapentine, clarithromycin, clofazimine and ethambutol, was evaluated in the beige mouse (C57BL/6J--bgj/bgj) model of disseminated Mycobacterium avium infection."( TLC G-65 in combination with other agents in the therapy of Mycobacterium avium infection in beige mice.
Cynamon, MH; Klemens, SP; Swenson, CE, 1992
)
" This study aimed to examine pharmacokinetic drug-drug interactions between this regimen and dolutegravir, a first-line antiretroviral medication."( Cytokine-Mediated Systemic Adverse Drug Reactions in a Drug-Drug Interaction Study of Dolutegravir With Once-Weekly Isoniazid and Rifapentine.
Alfaro, RM; Brooks, KM; De, P; Dobos, KM; George, JM; Hadigan, C; Kellogg, A; Kovacs, JA; Kumar, P; McLaughlin, M; McManus, M; Mehaffy, C; Pau, AK; Rupert, A, 2018
)
"This was a single-center, open-label, fixed-sequence, drug-drug interaction study in healthy volunteers."( Cytokine-Mediated Systemic Adverse Drug Reactions in a Drug-Drug Interaction Study of Dolutegravir With Once-Weekly Isoniazid and Rifapentine.
Alfaro, RM; Brooks, KM; De, P; Dobos, KM; George, JM; Hadigan, C; Kellogg, A; Kovacs, JA; Kumar, P; McLaughlin, M; McManus, M; Mehaffy, C; Pau, AK; Rupert, A, 2018
)

Bioavailability

The bioavailability of the Chinese drug was 74% of the Western drug. Results suggest that rifapentine delivery via ASD with these cellulosic polymers may improve bioavailability in vivo.

ExcerptReference
"25 mg/kg RPE, suggesting that FCE would be a better drug than RPE if its bioavailability could be improved, and that the levels following 16 mg/kg RPE were similar to those found in man after 8 mg/kg RPE taken with a fat-rich meal, suggesting good prospects for effective once-fortnightly human treatment."( Activity of two long-acting rifamycins, rifapentine and FCE 22807, in experimental murine tuberculosis.
Dhillon, J; Dickinson, JM; Guy, JA; Mitchison, DA; Ng, TK, 1992
)
"Assessment of the bioavailability of the Chinese rifapentine used in the trial."( Bioavailability of Chinese rifapentine during a clinical trial in Hong Kong.
Chan, SL; Dickinson, JM; Lam, CW; Mitchison, DA; Tam, CM, 1997
)
"An initial comparison of areas under curve obtained in a random allocation to 40 patients of rifapentine either of Western or Chinese origin indicated that the bioavailability of the Chinese drug was 74% of the Western drug."( Bioavailability of Chinese rifapentine during a clinical trial in Hong Kong.
Chan, SL; Dickinson, JM; Lam, CW; Mitchison, DA; Tam, CM, 1997
)
" Because of poor bioavailability of the rifapentine used (produced in China), its dose size was increased from 600 mg initially to about 750 mg in the last third of patients to obtain serum concentrations similar to those with rifapentine of Western origin; all doses were given after a meal promoting absorption."( Rifapentine and isoniazid in the continuation phase of treating pulmonary tuberculosis. Initial report.
Chan, SL; Kam, KM; Lam, CW; Leung, CC; Mitchison, DA; Morris, JS; Tam, CM, 1998
)
"Compared with an oral solution, the relative bioavailability of rifapentine is 70% following oral admninistration of tablets."( Rifapentine: its role in the treatment of tuberculosis.
Nahata, MC; Temple, ME, 1999
)
"A 15 mg/kg dose of RPT was well absorbed and well tolerated."( Consecutive-dose pharmacokinetics of rifapentine in patients diagnosed with pulmonary tuberculosis.
Langdon, G; McIlleron, H; Smith, PJ; Wilkins, JJ, 2004
)
"Macrocycles are ideal in efforts to tackle "difficult" targets, but our understanding of what makes them cell permeable and orally bioavailable is limited."( Macrocyclic drugs and clinical candidates: what can medicinal chemists learn from their properties?
Giordanetto, F; Kihlberg, J, 2014
)
" A previous rifapentine dose escalation study with daily dosing indicated a possible decrease in bioavailability as the dose increased and an increase in clearance over time for rifapentine and its active metabolite, desacetyl rifapentine."( Population pharmacokinetics of rifapentine and desacetyl rifapentine in healthy volunteers: nonlinearities in clearance and bioavailability.
Bliven-Sizemore, E; Burman, W; Dooley, KE; Dorman, SE; Lu, Y; Nuermberger, E; Savic, RM; Weiner, M, 2014
)
" Bioavailability decreases with increasing dose, yet high daily exposures are likely needed to improve efficacy and shorten the tuberculosis treatment duration."( Novel dosing strategies increase exposures of the potent antituberculosis drug rifapentine but are poorly tolerated in healthy volunteers.
Benson, CA; Cramer, Y; Dooley, KE; Dorman, SE; Haas, DW; Hafner, R; Hogg, E; Hovind, L; Janik, J; Marzinke, MA; Park, JG; Patterson, K; Savic, RM, 2015
)
" These results suggest that rifapentine delivery via ASD with these cellulosic polymers may improve bioavailability in vivo."( Cellulose-based amorphous solid dispersions enhance rifapentine delivery characteristics in vitro.
Edgar, KJ; Mosquera-Giraldo, LI; Neilson, AP; Nichols, BLB; Novo, DC; Taylor, LS; Winslow, CJ, 2018
)

Dosage Studied

No dosage adjustments are needed in patients with hepatic impairment. The optimum dosing regimen for rifapentine will have to be determined by controlled clinical trials.

ExcerptReference
" A dose-response experiment was performed with a daily rifapentine dose of 10, 20 or 40 mg/kg administered intraperitoneally."( Activity of rifapentine against Mycobacterium avium infection in beige mice.
Cynamon, MH; Klemens, SP, 1992
)
" Therapeutic activities of R-76-1 versus RMP and DL 473 versus RMP were compared, respectively, in the experimental infection of mice with Mycobacterium lepraemurium by different treatment schedules (immediate and delayed) and dosage regimens."( Antimycobacterial activities of two newer ansamycins, R-76-1 and DL 473.
Chen, JK; Hou, YH; Ji, BH; Lu, XZ; Ni, GX; Tang, QK; Wang, SY; Zhou, DH, 1986
)
" The activity of RPT was significantly enhanced when INH was added at the same dosing frequency."( Preventive therapy of tuberculosis with rifapentine in immunocompetent and nude mice.
Chapuis, L; Grosset, JH; Ji, B; O'Brien, RJ; Raviglione, MC; Truffot-Pernot, C, 1994
)
"The dose-response activity of rifabutin and the comparative activities of rifabutin and rifapentine were evaluated in the beige mouse model of disseminated Mycobacterium avium complex (MAC) infection."( Comparative in vivo activities of rifabutin and rifapentine against Mycobacterium avium complex.
Cynamon, MH; Grossi, MA; Klemens, SP, 1994
)
" These safety and pharmacokinetic results suggest that no dosage adjustments for rifapentine are needed in patients with hepatic impairment."( Pharmacokinetics of rifapentine in patients with varying degrees of hepatic dysfunction.
Eller, MG; Keung, AC; Weir, SJ, 1998
)
" Biliary excretion was the major route of elimination of radioactivity in bile duct-cannulated rats dosed either po or IV."( Disposition and metabolism of rifapentine, a rifamycin antibiotic, in mice, rats, and monkeys.
Emary, WB; Huh, K; Mathews, B; Toren, PC, 1998
)
"Because the aged-related changes in the pharmacokinetic profile of rifapentine observed in this study were modest and unlikely to be associated with toxicity, no dosage adjustments for this antibiotic are recommended in elderly patients."( Single-dose pharmacokinetics of rifapentine in elderly men.
Eller, MG; Keung, AC; Weir, SJ, 1998
)
" Based on these PK and safety data, no dosage adjustments for rifapentine based on gender are recommended."( Single-dose pharmacokinetics of rifapentine in women.
Eller, MG; Keung, AC; Weir, SJ, 1998
)
" Although food increased the exposure of these patients to rifapentine, the infrequent dosing schedule for the treatment of tuberculosis (e."( Pharmacokinetics of rifapentine in subjects seropositive for the human immunodeficiency virus: a phase I study.
Eller, MG; Keung, AC; Nicolau, DP; Nightingale, CH; Owens, RC; Weir, SJ, 1999
)
" The per cent increase in the ratio of 6beta-hydroxycortisol:cortisol following daily doses (+357%) was much higher compared with every 72-hour dosing (+236%)."( Enzyme induction observed in healthy volunteers after repeated administration of rifapentine and its lack of effect on steady-state rifapentine pharmacokinetics: part I.
Cheng, L; Eller, MG; Keung, A; McKenzie, KA; Reith, K; Weir, SJ, 1999
)
" In addition, the extended t(1/2) of rifapentine and its active metabolite support clinical investigation of once or twice-weekly rifapentine dosage regimens of rifapentine for the management of tuberculosis."( Single and multiple dose pharmacokinetics of rifapentine in man: part II.
Eller, MG; Keung, A; McKenzie, KA; Weir, SJ, 1999
)
" Its efficacy at the currently approved dosage of 600 mg may be slightly lower than that of rifampin."( Rifapentine: its role in the treatment of tuberculosis.
Nahata, MC; Temple, ME, 1999
)
" The optimum dosing regimen for rifapentine will have to be determined by controlled clinical trials."( Single-dose intrapulmonary pharmacokinetics of rifapentine in normal subjects.
Conte, JE; Golden, JA; Kipps, J; Lin, ET; McQuitty, M; Zurlinden, E, 2000
)
" Administered as single doses, MXFX in a dosage of 150 mg per kg was more active than OFLO in the same dosage, and displayed the same level of activity as RMP in a dosage of 10 mg per kg; the combination MXFX-minocycline (MINO) (MM) was more bactericidal than the combination OFLO-MINO (OM); RPT in a dosage of 10 mg per kg was more bactericidal than RMP administered in the same dosage, and even more active than the combination RMP-OFLO-MINO (ROM); the combination RPT-MXFX-MINO (PMM) killed 99."( Combination of rifapentine-moxifloxacin-minocycline (PMM) for the treatment of leprosy.
Grosset, J; Ji, B, 2000
)
" Further studies with increased rifapentine dosage are necessary."( Rifapentine and isoniazid in the continuation phase of a 6-month regimen. Final report at 5 years: prognostic value of various measures.
Chan, SL; Goodall, RL; Kam, KM; Mitchison, DA; Tam, CM, 2002
)
" Rifapentine 900-mg, once-weekly dosing appears to be safe and well tolerated and is being evaluated in Phase III efficacy trials of treatment of latent tuberculosis."( A prospective, randomized, double-blind study of the tolerability of rifapentine 600, 900, and 1,200 mg plus isoniazid in the continuation phase of tuberculosis treatment.
Bock, NN; Conwell, DS; Hamilton, CD; Mosher, A; Pachucki, C; Samuels, M; Sterling, TR; Vernon, A; Wang, YC, 2002
)
" We evaluated with the same model similar regimens in which we increased the dosing of rifapentine from 10 to 15 mg/kg of body weight and of moxifloxacin from 100 to 400 mg/kg."( Efficient intermittent rifapentine-moxifloxacin-containing short-course regimen for treatment of tuberculosis in mice.
Chauffour, A; Jarlier, V; Lounis, N; Truffot-Pernot, C; Veziris, N, 2005
)
" Patients were included in the study if they had been receiving first-line antimycobacterial therapy (rifampin, isoniazid, pyrazinamide, and ethambutol) for not less than 4 weeks and not more than 6 weeks and were divided into three RFP dosage groups based on weight: 600 mg, <45 kg; 750 mg, 46 to 55 kg; and 900 mg, >55 kg."( Population pharmacokinetics of rifapentine and its primary desacetyl metabolite in South African tuberculosis patients.
Langdon, G; McFadyen, L; McIlleron, H; Simonsson, US; Smith, P; Wilkins, J, 2005
)
" Hence, the study suggests that co-administration of Rp and H should be avoided, like in case of R and H, and the two drugs should not be formulated directly into a single dosage form."( Study of the interaction between rifapentine and isoniazid under acid conditions.
Bhutani, H; Prasad, B; Singh, S, 2006
)
"A significant difference in dose-normalized area under the curves (AUC0-n and AUC0-infinity) was observed between children receiving the 150 and 300 mg doses, which was accounted for by differences in age between the dosing arms."( Pharmacokinetics of rifapentine in children.
Abdel-Rahman, SM; Blake, MJ; Jacobs, RF; Kearns, GL; Lowery, NK; Sterling, TR, 2006
)
" As meal behavior has a substantial impact on rifapentine exposure, it should be considered in the evaluation of optimal dosing approaches."( Effects of four different meal types on the population pharmacokinetics of single-dose rifapentine in healthy male volunteers.
Fourie, PB; McIlleron, HM; Mitchison, D; Roscigno, G; Simonsson, US; Smith, PJ; Van Der Walt, JS; Zvada, SP, 2010
)
" Daily dosing of rifapentine (P), a potent rifamycin with high intracellular accumulation, in place of rifampin (R) in the standard antitubercular regimen significantly shortens the duration of treatment needed to prevent relapse in a murine model of active TB."( Rifapentine is not more active than rifampin against chronic tuberculosis in guinea pigs.
Dutta, NK; Grosset, JH; Illei, PB; Karakousis, PC; Mdluli, KE; Nuermberger, EL; Peloquin, CA; Pinn, ML, 2012
)
" Rifapentine, a rifamycin antibiotic, is currently approved for intermittent dosing in the treatment of TB."( An update on the use of rifapentine for tuberculosis therapy.
Bai, X; Chan, JG; Traini, D, 2014
)
"Recent murine studies found that rifapentine, dosed daily, at least halved tuberculosis treatment times compared with standard rifampicin and isoniazid-containing regimens."( A novel inhalable form of rifapentine.
Britton, WJ; Chan, HK; Chan, JC; Chan, JG; Duke, CC; Ong, HX; Traini, D; Tyne, AS; Young, PM, 2014
)
" A previous rifapentine dose escalation study with daily dosing indicated a possible decrease in bioavailability as the dose increased and an increase in clearance over time for rifapentine and its active metabolite, desacetyl rifapentine."( Population pharmacokinetics of rifapentine and desacetyl rifapentine in healthy volunteers: nonlinearities in clearance and bioavailability.
Bliven-Sizemore, E; Burman, W; Dooley, KE; Dorman, SE; Lu, Y; Nuermberger, E; Savic, RM; Weiner, M, 2014
)
" Simulations indicated that increasing the bedaquiline dosage to mitigate the interaction would yield elevated M2 concentrations during the first treatment weeks."( Rifampicin and rifapentine significantly reduce concentrations of bedaquiline, a new anti-TB drug.
Dooley, KE; Karlsson, MO; Murray, S; Svensson, EM, 2015
)
" In arm 1, rifapentine was administered at 10 mg/kg of body weight twice daily and 20 mg/kg once daily, each for 14 days, separated by a 28-day washout; the dosing sequence was randomized."( Novel dosing strategies increase exposures of the potent antituberculosis drug rifapentine but are poorly tolerated in healthy volunteers.
Benson, CA; Cramer, Y; Dooley, KE; Dorman, SE; Haas, DW; Hafner, R; Hogg, E; Hovind, L; Janik, J; Marzinke, MA; Park, JG; Patterson, K; Savic, RM, 2015
)
" Further investigation is needed to determine the optimal dosage for loading rifapentine."( Treatment of Staphylococcus aureus-induced chronic osteomyelitis with bone-like hydroxyapatite/poly amino acid loaded with rifapentine microspheres.
Cao, ZD; Jiang, DM; Li, YJ; Wang, X; Wang, ZL; Wu, J; Yan, L; Yi, YF, 2015
)
" Median rifapentine area under the concentration-time curve (AUC0-24) was 313 mcg*h/mL, similar to recent studies of rifapentine dosed at 450-600 mg daily."( A Phase 2 Randomized Trial of a Rifapentine plus Moxifloxacin-Based Regimen for Treatment of Pulmonary Tuberculosis.
Armstrong, DT; Barnes, GL; Cavalcante, SC; Chaisson, RE; Cohn, S; Conde, MB; Dalcolmo, M; Dooley, KE; Dorman, SE; Duarte, RS; Durovni, B; Efron, A; Loredo, C; Marzinke, MA; Mello, FC; Moulton, LH; Rolla, V; Savic, RM, 2016
)
" Based on these results, it is anticipated that the PBPK model developed in this study will be useful in evaluating dosing regimens for RPT and for characterizing tissue-level doses that could be predictors of problems related to efficacy or safety."( Physiologically Based Pharmacokinetic Model of Rifapentine and 25-Desacetyl Rifapentine Disposition in Humans.
Eppers, GJ; Reisfeld, B; Zurlinden, TJ, 2016
)
" The effectiveness of weekly dosing with inhalable rifapentine will be assessed in murine Mycobacterium tuberculosis infection."( Inhalation of Respirable Crystalline Rifapentine Particles Induces Pulmonary Inflammation.
Ashhurst, AS; Britton, WJ; Chan, HK; Nagalingam, G; Parumasivam, T, 2017
)
" Combinations of optimal dose and release rates were simulated such that plasma concentrations were maintained over the epidemiological cut-off or minimum inhibitory concentration for the dosing interval."( Modelling the long-acting administration of anti-tuberculosis agents using PBPK: a proof of concept study.
Flexner, C; Moss, DM; Owen, A; Podany, AT; Rajoli, RKR; Siccardi, M; Swindells, S, 2018
)
" The aim of this work was to develop and characterise rifapentine (RPT)-loaded PLGA-based nanoparticles (NPs) for reducing dosing frequency."( Development of Rifapentine-Loaded PLGA-Based Nanoparticles: In vitro Characterisation and in vivo Study in Mice.
Chen, J; Li, X; Liang, Q; Luo, C; Ma, X; Song, X; Tian, Z; Xiang, H; Zhao, W, 2020
)
"The application of PLGA-based NPs as sustained-release delivery vehicles for RPT could prolong drug release, modify pharmacokinetics, increase antitubercular activity and diminish toxicity, thereby allowing low dosage and frequency."( Development of Rifapentine-Loaded PLGA-Based Nanoparticles: In vitro Characterisation and in vivo Study in Mice.
Chen, J; Li, X; Liang, Q; Luo, C; Ma, X; Song, X; Tian, Z; Xiang, H; Zhao, W, 2020
)
" Dosing was according to participant bodyweight."( Safety and feasibility of 1 month of daily rifapentine plus isoniazid to prevent tuberculosis in children and adolescents: a prospective cohort study.
Amanullah, F; Becerra, MC; Fareed, U; Farooq, S; Hussain, H; Jaswal, M; Keshavjee, S; Khan, AJ; Khan, H; Malik, AA; Nasir, K; Safdar, N; Shahbaz, S, 2021
)
" We used a validated paucibacillary mouse model of TPT in combination with dynamic oral dosing of both drugs to simulate and understand exposure-activity relationships to inform posology for future LAI formulations."( Using Dynamic Oral Dosing of Rifapentine and Rifabutin to Simulate Exposure Profiles of Long-Acting Formulations in a Mouse Model of Tuberculosis Preventive Therapy.
Ammerman, NC; Betoudji, F; Chang, YS; Lee, J; Li, SY; Nuermberger, EL; Owen, A; Pertinez, H; Rannard, SP, 2023
)
" We provide suggested dolutegravir dosing considerations with concomitant rifapentine use, not currently addressed in recommended guidelines."( Alternative dolutegravir dosing strategies with concurrent rifapentine utilized for latent tuberculosis treatment.
Pecora Fulco, P; Taylor, A; Winthrop, E, 2023
)
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (2)

RoleDescription
antitubercular agentA substance that kills or slows the growth of Mycobacterium tuberculosis and is used in the treatment of tuberculosis.
leprostatic drugA substance that suppresses Mycobacterium leprae, ameliorates the clinical manifestations of leprosy, and/or reduces the incidence and severity of leprous reactions.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (3)

ClassDescription
rifamycins
N-alkylpiperazine
N-iminopiperazine
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (4)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
ATP-binding cassette sub-family C member 3Homo sapiens (human)IC50 (µMol)80.90000.63154.45319.3000AID1473740
Multidrug resistance-associated protein 4Homo sapiens (human)IC50 (µMol)35.90000.20005.677410.0000AID1473741
Bile salt export pumpHomo sapiens (human)IC50 (µMol)9.91000.11007.190310.0000AID1473738
Canalicular multispecific organic anion transporter 1Homo sapiens (human)IC50 (µMol)16.30002.41006.343310.0000AID1473739
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (41)

Processvia Protein(s)Taxonomy
xenobiotic metabolic processATP-binding cassette sub-family C member 3Homo sapiens (human)
xenobiotic transmembrane transportATP-binding cassette sub-family C member 3Homo sapiens (human)
bile acid and bile salt transportATP-binding cassette sub-family C member 3Homo sapiens (human)
glucuronoside transportATP-binding cassette sub-family C member 3Homo sapiens (human)
xenobiotic transportATP-binding cassette sub-family C member 3Homo sapiens (human)
transmembrane transportATP-binding cassette sub-family C member 3Homo sapiens (human)
leukotriene transportATP-binding cassette sub-family C member 3Homo sapiens (human)
monoatomic anion transmembrane transportATP-binding cassette sub-family C member 3Homo sapiens (human)
transport across blood-brain barrierATP-binding cassette sub-family C member 3Homo sapiens (human)
prostaglandin secretionMultidrug resistance-associated protein 4Homo sapiens (human)
cilium assemblyMultidrug resistance-associated protein 4Homo sapiens (human)
platelet degranulationMultidrug resistance-associated protein 4Homo sapiens (human)
xenobiotic metabolic processMultidrug resistance-associated protein 4Homo sapiens (human)
xenobiotic transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
bile acid and bile salt transportMultidrug resistance-associated protein 4Homo sapiens (human)
prostaglandin transportMultidrug resistance-associated protein 4Homo sapiens (human)
urate transportMultidrug resistance-associated protein 4Homo sapiens (human)
glutathione transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
cAMP transportMultidrug resistance-associated protein 4Homo sapiens (human)
leukotriene transportMultidrug resistance-associated protein 4Homo sapiens (human)
monoatomic anion transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
export across plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
transport across blood-brain barrierMultidrug resistance-associated protein 4Homo sapiens (human)
guanine nucleotide transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
fatty acid metabolic processBile salt export pumpHomo sapiens (human)
bile acid biosynthetic processBile salt export pumpHomo sapiens (human)
xenobiotic metabolic processBile salt export pumpHomo sapiens (human)
xenobiotic transmembrane transportBile salt export pumpHomo sapiens (human)
response to oxidative stressBile salt export pumpHomo sapiens (human)
bile acid metabolic processBile salt export pumpHomo sapiens (human)
response to organic cyclic compoundBile salt export pumpHomo sapiens (human)
bile acid and bile salt transportBile salt export pumpHomo sapiens (human)
canalicular bile acid transportBile salt export pumpHomo sapiens (human)
protein ubiquitinationBile salt export pumpHomo sapiens (human)
regulation of fatty acid beta-oxidationBile salt export pumpHomo sapiens (human)
carbohydrate transmembrane transportBile salt export pumpHomo sapiens (human)
bile acid signaling pathwayBile salt export pumpHomo sapiens (human)
cholesterol homeostasisBile salt export pumpHomo sapiens (human)
response to estrogenBile salt export pumpHomo sapiens (human)
response to ethanolBile salt export pumpHomo sapiens (human)
xenobiotic export from cellBile salt export pumpHomo sapiens (human)
lipid homeostasisBile salt export pumpHomo sapiens (human)
phospholipid homeostasisBile salt export pumpHomo sapiens (human)
positive regulation of bile acid secretionBile salt export pumpHomo sapiens (human)
regulation of bile acid metabolic processBile salt export pumpHomo sapiens (human)
transmembrane transportBile salt export pumpHomo sapiens (human)
xenobiotic metabolic processCanalicular multispecific organic anion transporter 1Homo sapiens (human)
xenobiotic transmembrane transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
negative regulation of gene expressionCanalicular multispecific organic anion transporter 1Homo sapiens (human)
bile acid and bile salt transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
bilirubin transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
heme catabolic processCanalicular multispecific organic anion transporter 1Homo sapiens (human)
xenobiotic export from cellCanalicular multispecific organic anion transporter 1Homo sapiens (human)
transmembrane transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
transepithelial transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
leukotriene transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
monoatomic anion transmembrane transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
transport across blood-brain barrierCanalicular multispecific organic anion transporter 1Homo sapiens (human)
xenobiotic transport across blood-brain barrierCanalicular multispecific organic anion transporter 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (24)

Processvia Protein(s)Taxonomy
ATP bindingATP-binding cassette sub-family C member 3Homo sapiens (human)
ABC-type xenobiotic transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
glucuronoside transmembrane transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ABC-type glutathione S-conjugate transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ABC-type bile acid transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ATP hydrolysis activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ATPase-coupled transmembrane transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
xenobiotic transmembrane transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ATPase-coupled inorganic anion transmembrane transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
icosanoid transmembrane transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ABC-type transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
guanine nucleotide transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
protein bindingMultidrug resistance-associated protein 4Homo sapiens (human)
ATP bindingMultidrug resistance-associated protein 4Homo sapiens (human)
ABC-type xenobiotic transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
prostaglandin transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
urate transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
purine nucleotide transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ABC-type glutathione S-conjugate transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ABC-type bile acid transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
efflux transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
15-hydroxyprostaglandin dehydrogenase (NAD+) activityMultidrug resistance-associated protein 4Homo sapiens (human)
ATP hydrolysis activityMultidrug resistance-associated protein 4Homo sapiens (human)
glutathione transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ATPase-coupled transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
xenobiotic transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ATPase-coupled inorganic anion transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ABC-type transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
protein bindingBile salt export pumpHomo sapiens (human)
ATP bindingBile salt export pumpHomo sapiens (human)
ABC-type xenobiotic transporter activityBile salt export pumpHomo sapiens (human)
bile acid transmembrane transporter activityBile salt export pumpHomo sapiens (human)
canalicular bile acid transmembrane transporter activityBile salt export pumpHomo sapiens (human)
carbohydrate transmembrane transporter activityBile salt export pumpHomo sapiens (human)
ABC-type bile acid transporter activityBile salt export pumpHomo sapiens (human)
ATP hydrolysis activityBile salt export pumpHomo sapiens (human)
protein bindingCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ATP bindingCanalicular multispecific organic anion transporter 1Homo sapiens (human)
organic anion transmembrane transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ABC-type xenobiotic transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
bilirubin transmembrane transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ABC-type glutathione S-conjugate transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ATP hydrolysis activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ATPase-coupled transmembrane transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
xenobiotic transmembrane transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ATPase-coupled inorganic anion transmembrane transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ABC-type transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (17)

Processvia Protein(s)Taxonomy
plasma membraneATP-binding cassette sub-family C member 3Homo sapiens (human)
basal plasma membraneATP-binding cassette sub-family C member 3Homo sapiens (human)
basolateral plasma membraneATP-binding cassette sub-family C member 3Homo sapiens (human)
membraneATP-binding cassette sub-family C member 3Homo sapiens (human)
nucleolusMultidrug resistance-associated protein 4Homo sapiens (human)
Golgi apparatusMultidrug resistance-associated protein 4Homo sapiens (human)
plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
membraneMultidrug resistance-associated protein 4Homo sapiens (human)
basolateral plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
apical plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
platelet dense granule membraneMultidrug resistance-associated protein 4Homo sapiens (human)
external side of apical plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
basolateral plasma membraneBile salt export pumpHomo sapiens (human)
Golgi membraneBile salt export pumpHomo sapiens (human)
endosomeBile salt export pumpHomo sapiens (human)
plasma membraneBile salt export pumpHomo sapiens (human)
cell surfaceBile salt export pumpHomo sapiens (human)
apical plasma membraneBile salt export pumpHomo sapiens (human)
intercellular canaliculusBile salt export pumpHomo sapiens (human)
intracellular canaliculusBile salt export pumpHomo sapiens (human)
recycling endosomeBile salt export pumpHomo sapiens (human)
recycling endosome membraneBile salt export pumpHomo sapiens (human)
extracellular exosomeBile salt export pumpHomo sapiens (human)
membraneBile salt export pumpHomo sapiens (human)
plasma membraneCanalicular multispecific organic anion transporter 1Homo sapiens (human)
cell surfaceCanalicular multispecific organic anion transporter 1Homo sapiens (human)
apical plasma membraneCanalicular multispecific organic anion transporter 1Homo sapiens (human)
intercellular canaliculusCanalicular multispecific organic anion transporter 1Homo sapiens (human)
apical plasma membraneCanalicular multispecific organic anion transporter 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (59)

Assay IDTitleYearJournalArticle
AID1474167Liver toxicity in human assessed as induction of drug-induced liver injury by measuring verified drug-induced liver injury concern status2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID580855Plasma protein binding in healthy human at 600 mg/kg, po2009Antimicrobial agents and chemotherapy, Mar, Volume: 53, Issue:3
New drugs against tuberculosis: problems, progress, and evaluation of agents in clinical development.
AID570811Cmax in healthy human at 900 mg, po administered as a single dose measured on day 5 post compound dose by HPLC2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Repeated administration of high-dose intermittent rifapentine reduces rifapentine and moxifloxacin plasma concentrations.
AID570827Ratio of Volume of distribution in healthy human at 900 mg, po thrice weekly measured on day 19 post compound dose to Volume of distribution in healthy human at 900 mg, po administered as a single dose measured on day 102008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Repeated administration of high-dose intermittent rifapentine reduces rifapentine and moxifloxacin plasma concentrations.
AID580854Half life in healthy human at 600 mg/kg, po2009Antimicrobial agents and chemotherapy, Mar, Volume: 53, Issue:3
New drugs against tuberculosis: problems, progress, and evaluation of agents in clinical development.
AID625285Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic necrosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID570814Apparent oral clearance in healthy human at 900 mg, po administered as a single dose measured on day 5 post compound dose by HPLC2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Repeated administration of high-dose intermittent rifapentine reduces rifapentine and moxifloxacin plasma concentrations.
AID625291Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver function tests abnormal2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1473740Inhibition of human MRP3 overexpressed in Sf9 insect cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 10 mins by membrane vesicle transport assay2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID625287Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatomegaly2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1474102Drug concentration at steady state in human at 600 mg administered twice weekly followed by 600 mg administered once in a week measured after 84 hrs2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID625280Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholecystitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1474105Ratio of drug concentration at steady state in human at 600 mg administered twice weekly followed by 600 mg administered once in a week measured after 84 hrs to IC50 for human MRP3 overexpressed in Sf9 insect cells2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID625289Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver disease2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625283Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for elevated liver function tests2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1473738Inhibition of human BSEP overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-taurocholate in presence of ATP measured after 15 to 20 mins by membrane vesicle transport assay2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID625286Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1474101AUC in human at 600 mg administered twice weekly followed by 600 mg administered once in a week measured after 84 hrs2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID625290Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver fatty2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1473739Inhibition of human MRP2 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID369451Antimicrobial activity against Staphylococcus epidermidis2007Antimicrobial agents and chemotherapy, Sep, Volume: 51, Issue:9
In vitro activities of different inhibitors of bacterial transcription against Staphylococcus epidermidis biofilm.
AID570812Tmax in healthy human at 900 mg, po administered as a single dose measured on day 5 post compound dose by HPLC2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Repeated administration of high-dose intermittent rifapentine reduces rifapentine and moxifloxacin plasma concentrations.
AID570817Cmax in healthy human at 900 mg, po thrice weekly measured on day 19 post compound dose by HPLC2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Repeated administration of high-dose intermittent rifapentine reduces rifapentine and moxifloxacin plasma concentrations.
AID625284Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic failure2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1473741Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID570813Half life in healthy human at 900 mg, po administered as a single dose measured on day 5 post compound dose by HPLC2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Repeated administration of high-dose intermittent rifapentine reduces rifapentine and moxifloxacin plasma concentrations.
AID570819Half life in healthy human at 900 mg, po thrice weekly measured on day 19 post compound dose by HPLC2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Repeated administration of high-dose intermittent rifapentine reduces rifapentine and moxifloxacin plasma concentrations.
AID580853Tmax in healthy human at 600 mg/kg, po2009Antimicrobial agents and chemotherapy, Mar, Volume: 53, Issue:3
New drugs against tuberculosis: problems, progress, and evaluation of agents in clinical development.
AID580852Cmax in healthy human at 600 mg/kg, po2009Antimicrobial agents and chemotherapy, Mar, Volume: 53, Issue:3
New drugs against tuberculosis: problems, progress, and evaluation of agents in clinical development.
AID1474103Ratio of drug concentration at steady state in human at 600 mg administered twice weekly followed by 600 mg administered once in a week measured after 84 hrs to IC50 for human BSEP overexpressed in Sf9 insect cells2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID570820Apparent oral clearance in healthy human at 900 mg, po thrice weekly measured on day 19 post compound dose by HPLC2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Repeated administration of high-dose intermittent rifapentine reduces rifapentine and moxifloxacin plasma concentrations.
AID625288Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for jaundice2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625281Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholelithiasis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID580857Antimicrobial activity against rifampicin-sensitive Mycobacterium tuberculosis2009Antimicrobial agents and chemotherapy, Mar, Volume: 53, Issue:3
New drugs against tuberculosis: problems, progress, and evaluation of agents in clinical development.
AID570815Volume of distribution in healthy human at 900 mg, po administered as a single dose measured on day 5 post compound dose by HPLC2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Repeated administration of high-dose intermittent rifapentine reduces rifapentine and moxifloxacin plasma concentrations.
AID570821Volume of distribution in healthy human at 900 mg, po thrice weekly measured on day 19 post compound dose by HPLC2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Repeated administration of high-dose intermittent rifapentine reduces rifapentine and moxifloxacin plasma concentrations.
AID369459Inhibition of Staphylococcus epidermidis biofilm formation assessed as reduction of >2 log 10 bacterial count in biofilm after 24 hrs2007Antimicrobial agents and chemotherapy, Sep, Volume: 51, Issue:9
In vitro activities of different inhibitors of bacterial transcription against Staphylococcus epidermidis biofilm.
AID570824Ratio of Tmax in healthy human at 900 mg, po thrice weekly measured on day 19 post compound dose to Tmax in healthy human at 900 mg, po administered as a single dose measured on day 72008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Repeated administration of high-dose intermittent rifapentine reduces rifapentine and moxifloxacin plasma concentrations.
AID570818Tmax in healthy human at 900 mg, po thrice weekly measured on day 19 post compound dose by HPLC2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Repeated administration of high-dose intermittent rifapentine reduces rifapentine and moxifloxacin plasma concentrations.
AID570822Ratio of AUC (0 to 48 hrs) in healthy human at 900 mg, po thrice weekly measured on day 19 post compound dose to AUC (0 to 48 hrs) in healthy human at 900 mg, po administered as a single dose measured on day 5 post compound dose2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Repeated administration of high-dose intermittent rifapentine reduces rifapentine and moxifloxacin plasma concentrations.
AID369453Inhibition of Staphylococcus epidermidis RNA polymerase mediated transcription2007Antimicrobial agents and chemotherapy, Sep, Volume: 51, Issue:9
In vitro activities of different inhibitors of bacterial transcription against Staphylococcus epidermidis biofilm.
AID369457Inhibition of Staphylococcus epidermidis biofilm formation assessed as log 10 reduction of bacterial count in biofilm at 0.025 ug/ml per well after 24 hrs2007Antimicrobial agents and chemotherapy, Sep, Volume: 51, Issue:9
In vitro activities of different inhibitors of bacterial transcription against Staphylococcus epidermidis biofilm.
AID625279Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for bilirubinemia2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID369452Ratio of MBC for Staphylococcus epidermidis to MIC for Staphylococcus epidermidis2007Antimicrobial agents and chemotherapy, Sep, Volume: 51, Issue:9
In vitro activities of different inhibitors of bacterial transcription against Staphylococcus epidermidis biofilm.
AID580851AUC in healthy human at 600 mg/kg, po2009Antimicrobial agents and chemotherapy, Mar, Volume: 53, Issue:3
New drugs against tuberculosis: problems, progress, and evaluation of agents in clinical development.
AID570823Ratio of Cmax in healthy human at 900 mg, po thrice weekly measured on day 19 post compound dose to Cmax in healthy human at 900 mg, po administered as a single dose measured on day 62008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Repeated administration of high-dose intermittent rifapentine reduces rifapentine and moxifloxacin plasma concentrations.
AID570816AUC (0 to 48 hrs) in healthy human at 900 mg, po thrice weekly measured on day 19 post compound dose by HPLC2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Repeated administration of high-dose intermittent rifapentine reduces rifapentine and moxifloxacin plasma concentrations.
AID520108Antimicrobial activity against Mycobacterium tuberculosis H37Rv at assessed as growth inhibition at 10 mg/kg following 24 days oxygen depletion by Wayne method relative to control2008Antimicrobial agents and chemotherapy, Apr, Volume: 52, Issue:4
Evaluation of a 2-pyridone, KRQ-10018, against Mycobacterium tuberculosis in vitro and in vivo.
AID625292Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) combined score2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID570810AUC (0 to 48 hrs) in healthy human at 900 mg, po administered as a single dose measured on day 5 post compound dose by HPLC2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Repeated administration of high-dose intermittent rifapentine reduces rifapentine and moxifloxacin plasma concentrations.
AID580856Antimicrobial activity against rifampicin-resistant Mycobacterium tuberculosis2009Antimicrobial agents and chemotherapy, Mar, Volume: 53, Issue:3
New drugs against tuberculosis: problems, progress, and evaluation of agents in clinical development.
AID1065394Oral bioavailability in human2014Journal of medicinal chemistry, Jan-23, Volume: 57, Issue:2
Macrocyclic drugs and clinical candidates: what can medicinal chemists learn from their properties?
AID1474166Liver toxicity in human assessed as induction of drug-induced liver injury by measuring severity class index2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID1474104Ratio of drug concentration at steady state in human at 600 mg administered twice weekly followed by 600 mg administered once in a week measured after 84 hrs to IC50 for human MRP2 overexpressed in Sf9 insect cells2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID580858Ratio of AUC to MIC against Mycobacterium avium2009Antimicrobial agents and chemotherapy, Mar, Volume: 53, Issue:3
New drugs against tuberculosis: problems, progress, and evaluation of agents in clinical development.
AID625282Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cirrhosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1474106Ratio of drug concentration at steady state in human at 600 mg administered twice weekly followed by 600 mg administered once in a week measured after 84 hrs to IC50 for human MRP4 overexpressed in Sf9 insect cells2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID570825Ratio of Half life in healthy human at 900 mg, po thrice weekly measured on day 19 post compound dose to Half life in healthy human at 900 mg, po administered as a single dose measured on day 82008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Repeated administration of high-dose intermittent rifapentine reduces rifapentine and moxifloxacin plasma concentrations.
AID570826Ratio of Apparent oral clearance in healthy human at 900 mg, po thrice weekly measured on day 19 post compound dose to Apparent oral clearance in healthy human at 900 mg, po administered as a single dose measured on day 92008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Repeated administration of high-dose intermittent rifapentine reduces rifapentine and moxifloxacin plasma concentrations.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (392)

TimeframeStudies, This Drug (%)All Drugs %
pre-199029 (7.40)18.7374
1990's61 (15.56)18.2507
2000's56 (14.29)29.6817
2010's157 (40.05)24.3611
2020's89 (22.70)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials77 (19.06%)5.53%
Reviews50 (12.38%)6.00%
Case Studies7 (1.73%)4.05%
Observational7 (1.73%)0.25%
Other263 (65.10%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (53)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Efficacy of Risk-Targeted Video Based Directly on Observed Therapy for Latent TB[NCT03783728]0 participants (Actual)Observational2019-06-30Withdrawn(stopped due to Investigator is leaving the University)
Short Course Rifapentine and Isoniazid for the Preventive Treatment of Tuberculosis(SCRIPT-TB)[NCT03900858]566 participants (Anticipated)Interventional2018-12-01Recruiting
Six Weeks of Daily Rifapentine vs. a Comparator Arm of 12-16 Week Rifamycin-based Treatment of Latent M. Tuberculosis Infection: Assessment of Safety, Tolerability and Effectiveness[NCT03474029]Phase 2/Phase 33,400 participants (Anticipated)Interventional2019-08-01Recruiting
Safety and Tolerability of Ultra-short Course Rifapentine and Isoniazid (1HP) for Prevention of Tuberculosis in HIV-Uninfected Individuals[NCT04703075]Phase 4500 participants (Anticipated)Interventional2022-03-24Recruiting
Addiction, HIV and Tuberculosis in Malaysian Criminal Justice Settings[NCT03089983]1,129 participants (Actual)Interventional2017-08-21Active, not recruiting
Prospective Randomized Study to Compare Clinical Outcomes in Patients With Osteomyelitis Treated With Intravenous Antibiotics Versus Intravenous Antibiotics With an Early Switch to Oral Antibiotics[NCT02099240]Early Phase 111 participants (Actual)Interventional2014-03-06Terminated(stopped due to Not enough patient enrollment and lack of staffing)
Evaluation of the Efficacy and Safety of a Short-course, Daily, 4-month Regimen Including Isoniazid, Pyrazinamide, Rifapentine and Moxifloxacin (2HZPM/2HPM) for the Treatment of Drug-susceptible Pulmonary Tuberculosis in Taiwan (ESCAPE-TB)[NCT04856644]Phase 3366 participants (Anticipated)Interventional2021-05-01Not yet recruiting
TB YOUTH - TB sYstemic Management Using One-month, Ultra-short TPT Regimen for scHool Contacts[NCT06022146]Phase 33,520 participants (Anticipated)Interventional2023-09-01Recruiting
A Randomized Double Blind Placebo Controlled Trial of Rifapentine and Isoniazid for Prevention of Tuberculosis in People With Diabetes[NCT04600167]Phase 33,000 participants (Anticipated)Interventional2022-06-17Recruiting
TBTC Study 31 PK/PD: Population Pharmacokinetic and Pharmacodynamic Study of Efficacy and Safety of High-Dose Rifapentine and Moxifloxacin for Treatment of Tuberculosis in the Study 31 Treatment Trial: Intensive PK Sampling[NCT02563327]Phase 360 participants (Anticipated)Interventional2016-05-30Recruiting
TBTC Study 29: Evaluation of a Rifapentine-containing Regimen for Intensive Phase Treatment of Pulmonary Tuberculosis[NCT00694629]Phase 2865 participants (Actual)Interventional2008-12-31Completed
One-month Latent Tuberculosis Treatment for Renal Transplant Candidates[NCT05411744]Phase 425 participants (Anticipated)Interventional2022-07-01Recruiting
Toward a Safe and Reachable Preventive Therapy for LTBI: a Multicenter Randomized Controlled Study in Taiwan[NCT02208427]Phase 3283 participants (Actual)Interventional2014-08-31Active, not recruiting
Impact of Weekly Administration of Rifapentine and Isoniazid on Steady State Pharmacokinetics of Tenofovir Alafenamide in Healthy Volunteers[NCT03510468]Phase 151 participants (Actual)Interventional2018-06-12Completed
TBTC Study 26: Effectiveness and Tolerability of Weekly Rifapentine/Isoniazid for 3 Months Versus Daily Isoniazid for 9 Months for the Treatment of Latent Tuberculosis Infection[NCT00023452]Phase 38,053 participants (Actual)Interventional2001-06-30Completed
Acceptability and Completion Rates of a New 12 Dose Treatment (3 Month) Compared to the Standard Treatment for Latent TB Infection Treatment[NCT02689089]Phase 4182 participants (Actual)Interventional2016-11-28Completed
Pharmacokinetic and Pharmacodynamic Studies of Efficacy, Tolerability and Safety of Higher Dosage Rifapentine for Treatment of Tuberculosis[NCT01043575]Phase 260 participants (Actual)Interventional2009-04-30Completed
A Randomized, Partially-blinded, Clinical Trial of Isoniazid and Rifapentine (3HP) Therapy to Prevent Pulmonary Tuberculosis in High-risk Individuals Identified by a Transcriptomic Correlate of Risk[NCT02735590]Phase 2/Phase 32,927 participants (Actual)Interventional2016-09-20Active, not recruiting
Phase III Clinical Trial of Ultra-Short-Course Rifapentine/Isoniazid for the Prevention of Active Tuberculosis in HIV-Infected Individuals With Latent Tuberculosis Infection[NCT01404312]Phase 33,000 participants (Actual)Interventional2012-05-23Completed
The Effect of Rifapentine on Plasma Concentrations of Raltegravir[NCT00809718]Phase 127 participants (Actual)Interventional2009-02-28Completed
Phase I Dose Escalation Study of the Pharmacokinetics, Safety and Tolerability of Rifapentine and the Effects of Increasing Doses of Rifapentine on Induction of Metabolizing Enzymes in Healthy Volunteers[NCT01162486]Phase 137 participants (Actual)Interventional2010-04-30Completed
A Study of the Pharmacokinetic and Pharmacodynamic Interactions Between Bictegravir, Tenofovir Alafenamide and Rifapentine in Healthy Adult Subjects[NCT04551573]Phase 40 participants (Actual)Interventional2021-05-31Withdrawn(stopped due to COVID-19 Pandemic)
A Phase I Open-label Trial to Investigate the Pharmacokinetic Interaction Between Rifapentine or Rifampicin and a Single Dose of TMC207 in Healthy Subjects[NCT02216331]Phase 132 participants (Actual)Interventional2010-03-31Completed
A Randomised Controlled Trial of a 12-dose Rifapentine and Isoniazid (RPT+INH) Regimen Using Direct Observed Therapy (DOT) Versus 6 Months of Daily Isoniazid for Latent Tuberculosis Infection (LTBI) in Socially Marginalised People[NCT03266991]Phase 422 participants (Actual)Interventional2017-10-27Terminated(stopped due to Recruitment issues)
A Phase IIc Trial of Clofazimine- and Rifapentine-Containing Treatment Shortening Regimens in Drug-Susceptible Tuberculosis: The CLO-FAST Study[NCT04311502]Phase 2104 participants (Actual)Interventional2021-06-16Active, not recruiting
Role of Short Course Rifapentine and Isoniazid for the Preventive Treatment for Latent Genital Tuberculosis in Women With Recurrent Implantation Failure: A Prospective Interventional Cohort Study[NCT04528277]Phase 31,050 participants (Anticipated)Interventional2020-09-01Not yet recruiting
TBTC Study 26 PK: Rifapentine Pharmacokinetics in Children Receiving Once Weekly Rifapentine and Isoniazid for the Treatment of Latent Tuberculosis Infection[NCT00164450]230 participants (Anticipated)Interventional2005-09-30Completed
A Phase 2 Randomized, Open-label Trial of Daily Rifapentine 450mg or 600mg in Place of Rifampicin 600mg for Intensive Phase Treatment of Smear-positive Pulmonary Tuberculosis[NCT00814671]Phase 2153 participants (Actual)Interventional2010-04-30Completed
Phase I/II Dose Finding and Safety Study of Rifapentine and Isoniazid in HIV-Infected and HIV-Uninfected Children With Latent Tuberculosis Infection[NCT03730181]Phase 1/Phase 272 participants (Anticipated)Interventional2019-10-12Recruiting
Pharmacokinetic Issues in the Use of Moxifloxacin Plus Rifapentine[NCT00460759]Phase 115 participants (Actual)Interventional2007-06-30Terminated
Comparing Incidence Rate of Systemic Drug Reactions Under 3HP and 1HP Regimen for Latent Tuberculosis Infection Treatment: a Pragmatic Multicenter Randomized Control Trial[NCT04094012]Phase 3490 participants (Actual)Interventional2019-09-24Completed
Tolerance, Safety, and Activity of Rifapentine Alone and in Combination Therapy in AIDS Patients With Mycobacterium Avium Complex Bacteremia.[NCT00002192]Phase 20 participants InterventionalCompleted
TBTC Study 22: Efficacy and Safety of Once-Weekly Rifapentine and Isoniazid Compared to Efficacy and Safety of Once-Weekly Rifapentine and Isoniazid Compared to Twice-Weekly Rifampin and Isoniazid in the Continuation Phase of Therapy for Pulmonary Tubercu[NCT00023335]Phase 31,000 participants Interventional1995-04-30Completed
Safety and Tolerability of 1 Month Daily (1HP) and 3 Months Weekly (3HP) Isoniazid and Rifapentine With Pharmacokinetics of Dolutegravir (DTG) in Pregnant People With HIV[NCT05122026]Phase 1/Phase 2252 participants (Anticipated)Interventional2023-01-30Not yet recruiting
Intensive Pharmacokinetic Study of Three Doses of Rifapentine (600, 900 and 1200mg) During Continuation Phase Therapy of Tuberculosis in HIV-Negative Adults[NCT00023387]36 participants Interventional2000-03-31Completed
TBTC Study 25:A Prospective, Randomized, Double-Blind Study of the Tolerability of Higher Doses of Rifapentine[NCT00023426]Phase 2150 participants Interventional1999-07-31Completed
Novel TB Prevention Regimens for HIV-Infected Adults[NCT00057122]Phase 31,148 participants (Actual)Interventional2002-09-30Completed
Effectiveness and Tolerability of Weekly Rifapentine/Isoniazid for 3 Months for Tuberculosis Preventive Treatment: A Randomized Controlled Study in China[NCT02430259]Phase 3566 participants (Anticipated)Interventional2015-03-31Completed
A Phase II Randomized, Open-label Trial of a Rifapentine Plus Moxifloxacin-Based Regimen for Intensive Phase Treatment of Smear-Positive Pulmonary Tuberculosis[NCT00728507]Phase 2121 participants (Actual)Interventional2009-11-30Terminated(stopped due to Funding withdrawn)
Efficacy and Safety of Short-course Treatment for Drug-sensitive Tuberculosis in China[NCT05401071]Phase 2/Phase 32,442 participants (Anticipated)Interventional2023-01-13Recruiting
An Open-label, Non-randomized, Single Sequence, Two Periods, Four-treatment, Three Parallel Groups Pharmacokinetic Interaction Study of Repeated Oral Doses (Daily or Weekly Regimen) of Rifapentine on ATRIPLA™ (Fixed Dose Combination of Efavirenz, Emtricit[NCT01690403]Phase 125 participants (Actual)Interventional2012-12-31Completed
Implementation for Tuberculosis Preventive Therapy Among Latent Tuberculosis Infection in HIV-infected Individuals Using Novel Regimen of Isoniazid/Rifapentine Daily (4 Weeks) Compared to Isoniazid/Rifapentine Weekly (12 Weeks)[NCT03785106]Phase 32,500 participants (Anticipated)Interventional2019-08-15Recruiting
A Phase I/II Trial of the Pharmacokinetics, Tolerability, and Safety of Once-Weekly Rifapentine and Isoniazid in HIV-1-infected and HIV-1-uninfected Pregnant and Postpartum Women With Latent Tuberculosis Infection[NCT02651259]Phase 1/Phase 250 participants (Actual)Interventional2017-03-13Completed
A Randomised, Pragmatic, Open-Label Trial To Evaluate The Effect Of Three Months Of High Dose Rifapentine Plus Isoniazid Administered As A Single Round Or Given Annually In HIV-Positive Individuals[NCT02980016]Phase 34,027 participants (Actual)Interventional2016-11-30Completed
A Randomized Controlled Non-Inferiority Study for Shortening Tuberculosis Treatment With Sitafloxacin-Containing Regimens[NCT05454345]Phase 3620 participants (Anticipated)Interventional2022-10-01Not yet recruiting
A Phase 1, Open-Label, Fixed-Sequence, Drug Interaction Study to Investigate the Effect of Once-Weekly Rifapentine and Isoniazid on the Pharmacokinetics of Steady-State Doravirine[NCT03886701]Phase 111 participants (Actual)Interventional2019-04-22Completed
Phase I Clinical Trial of the Pharmacokinetics of High-dose Daily Rifapentine, Given as a Single Dose or in Divided Doses to Healthy Volunteers[NCT01574638]Phase 144 participants (Actual)Interventional2012-06-30Completed
TBTC Study 33. An Evaluation of Adherence to Latent Tuberculosis Infection (LTBI) Treatment With 12 Doses of Once Weekly Rifapentine (RPT) and Isoniazid (INH) Given as Self-administered (SAT) Versus Directly-observed Therapy (DOT): iAdhere.[NCT01582711]Phase 31,002 participants (Actual)Interventional2012-09-30Completed
Two-month Regimens Using Novel Combinations to Augment Treatment Effectiveness for Drug-sensitive Tuberculosis[NCT03474198]Phase 2/Phase 3675 participants (Actual)Interventional2018-03-21Completed
Comparison of 3-month Once-weekly Isoniazid Plus Rifapentine, 4-month Daily Rifampicin, and 3-month Daily Isoniazid Plus Rifampicin for the Treatment Latent Tuberculosis in Patients With End-stage Kidney Disease: A Randomised Clinical Trial[NCT05021731]Phase 4225 participants (Anticipated)Interventional2022-04-01Not yet recruiting
"A Randomized Trial Comparing Treatment Completion of Daily Rifapentine & Isoniazid for One Month (1HP) To Weekly Rifapentine & Isoniazid For 3 Months (3HP) In Persons Living With HIV and in HIV-negative Household Contacts of Recently Diagnosed Tuberculos[NCT05118490]Phase 41,000 participants (Anticipated)Interventional2023-04-01Not yet recruiting
Drug-Drug Interactions Between Rifapentine and Dolutegravir in HIV/LTBI Co-Infected Individuals[NCT04272242]Phase 272 participants (Anticipated)Interventional2020-08-01Suspended(stopped due to Following completion of Arm 1, A5372 is currently Temporarily Closed. Timeline for opening of Arm 2 is not available.)
Rifapentine-containing Treatment Shortening Regimens for Pulmonary Tuberculosis: A Randomized, Open-label, Controlled Phase 3 Clinical Trial. TBTC Study 31, ACTG Study A5349[NCT02410772]Phase 32,516 participants (Actual)Interventional2016-01-25Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00023452 (10) [back to overview]Percentage of Participants With Death Due to Any Cause
NCT00023452 (10) [back to overview]Cumulative Rate of Culture-Confirmed or Probable (Clinical) TB Disease (Regardless of Age) At 33 Months After Enrollment
NCT00023452 (10) [back to overview]Cumulative Rate of Culture-Confirmed TB Disease in Participants ≥18 Years of Age AND Culture Confirmed or Probable (Clinical) TB Disease Among Participants <18 Years of Age Who Completed Study Phase Therapy Within 33 Months of Enrollment
NCT00023452 (10) [back to overview]Cumulative Rate of Culture-Confirmed TB Disease in Participants ≥18 Years of Age AND Culture-Confirmed or Probable (Clinical) TB Disease in Participants <18 Years of Age at 24 Months Following Completion of Study Therapy
NCT00023452 (10) [back to overview]Cumulative Rate of Culture-Confirmed TB Disease in Participants ≥18 Years of Age AND Culture-Confirmed or Probable (Clinical) TB Disease in Participants Less Than [<]18 Years of Age at 33 Months After Enrollment
NCT00023452 (10) [back to overview]Percentage of Participants Who Completed the Treatment Regimen
NCT00023452 (10) [back to overview]Percentage of Participants With Drug Discontinuation Due to Adverse Drug Reactions Associated With 3RPT/INH or 9INH
NCT00023452 (10) [back to overview]Percentage of Participants With Drug Discontinuation for Any Reason Associated With 3RPT/INH or 9INH
NCT00023452 (10) [back to overview]Percentage of Participants With Resistance to Study Medications in Isolates of MTB From Participants Who Developed Active TB Disease Within 33 Months of Enrollment
NCT00023452 (10) [back to overview]Percentage of Patients With Grade 3 or 4 Drug Toxicities Associated With 3RPT/INH or 9INH
NCT00728507 (1) [back to overview]To Compare, by Treatment Group, the Percentage of Patients With a Negative Sputum Culture at the End of Intensive Phase Therapy.
NCT00814671 (5) [back to overview]Percentage of Participants With Negative Lowenstein Jensen Cultures at Week 8
NCT00814671 (5) [back to overview]Pharmacokinetics of Rifapentine
NCT00814671 (5) [back to overview]Time to Stable Culture Conversion on Liquid MGIT Media
NCT00814671 (5) [back to overview]Time to Stable Culture Conversion on Solid Medium
NCT00814671 (5) [back to overview]Tolerability
NCT01162486 (3) [back to overview]Number of Participants With Grade 2 or Higher Adverse Events Over the Course of the 26 Day Trial
NCT01162486 (3) [back to overview]Midazolam, AUC Over 12 Hours Post-dose
NCT01162486 (3) [back to overview]Pharmacokinetics (AUC of RPT Over 24 Hours Post-dose)
NCT01404312 (6) [back to overview]Cumulative Incidence of Death Due to a Non-TB Event
NCT01404312 (6) [back to overview]Incidence of First Diagnosis of Active Tuberculosis, Death Related to Tuberculosis, or Death From Unknown Cause
NCT01404312 (6) [back to overview]Cumulative Incidence of Death From Any Cause
NCT01404312 (6) [back to overview]Efavirenz (EFV) Plasma Concentrations in Arm A
NCT01404312 (6) [back to overview]Nevirapine (NVP) Plasma Concentrations in Arm A
NCT01404312 (6) [back to overview]Number of Participants With Antibiotic Resistance Among Mycobacterium Tuberculosis (MTB) Isolates in Participants Who Develop Active Tuberculosis
NCT02410772 (1) [back to overview]TB Disease-free Survival at 12M After Study Treatment Assignment Among Participants in Control Regimen, Regimen1 (2HRZE/4HR) to Experimental Regimens, Regimen3 (2HPZM/2HPM) and Regimen2 (2HPZ/2HP) (Assessable Population)
NCT02651259 (24) [back to overview]Absorption (ka) of INH
NCT02651259 (24) [back to overview]Absorption Rate Constant (ka) for Rifapentine (RPT)
NCT02651259 (24) [back to overview]Clearance Relative to Bioavailability (CL/F) for Rifapentine (RPT)
NCT02651259 (24) [back to overview]Clearance Relative to Bioavailability (CL/F) for Rifapentine (RPT) for Intensive and Sparse PK
NCT02651259 (24) [back to overview]Clearance Relative to Bioavailability (CLmet/F) for Desacetyl Rifapentine (Des-RPT)
NCT02651259 (24) [back to overview]Cord Blood Concentrations of Desacetyl Rifapentine (Des-RPT) Among Infants
NCT02651259 (24) [back to overview]Cord Blood Concentrations of Rifapentine (RPT) Among Infants
NCT02651259 (24) [back to overview]Incidence of Related Serious Adverse Events (SAEs) in Pregnant and Postpartum Women Taking Once-weekly RPT + INH
NCT02651259 (24) [back to overview]Number of Infants With Active TB up to 24 Weeks of Life
NCT02651259 (24) [back to overview]Number of Mothers With Active TB up to 24 Weeks Postpartum
NCT02651259 (24) [back to overview]Number of Participants With Discontinuation of Study Drug Due to Intolerance (Tolerability of Study Drug Regimen - i.e., RPT, INH, and Pyridoxine)
NCT02651259 (24) [back to overview]Percentage of Participants With All AEs Leading to Permanent Discontinuation of Study Drug Regimen (i.e., RPT, INH, and Pyridoxine)
NCT02651259 (24) [back to overview]Percentage of Participants With All Grade 3 and 4 AEs
NCT02651259 (24) [back to overview]Percentage of Participants With All Serious AEs
NCT02651259 (24) [back to overview]Percentage of Participants With Grade 2 Adverse Events (AEs) Judged to be Related to Study Drug Regimen
NCT02651259 (24) [back to overview]Percentage of Participants With Related Serious Adverse Events (AEs) in Infants Born to Women Taking Once-weekly RPT + INH
NCT02651259 (24) [back to overview]Plasma Concentrations of Rifapentine (RPT) Among Infants
NCT02651259 (24) [back to overview]Volume of Distribution of INH
NCT02651259 (24) [back to overview]Volume of Distribution Relative to Bioavailability (Vc/F) for Rifapentine (RPT)
NCT02651259 (24) [back to overview]Area Under the Curve From 0 to 24 Hours (AUC0-24) for RPT and Area Under the Curve From 0 to 24 Hours (AUC0-24) for Des-RPT Pregnant Women in 2nd and 3rd Trimester
NCT02651259 (24) [back to overview]Clearance (CL/F) of INH
NCT02651259 (24) [back to overview]Plasma Concentrations of Desacetyl Rifapentine (Des-RPT) Among Infants
NCT02651259 (24) [back to overview]Maximum Concentration (Cmin) for RPT and Maximum Concentration (Cmin) for Des-RPT Pregnant Women in 2nd and 3rd Trimester
NCT02651259 (24) [back to overview]Maximum Concentration (Cmax) for RPT Maximum Concentration (Cmax) for Des-RPT Pregnant Women in 2nd and 3rd Trimester
NCT03510468 (1) [back to overview]Plasma Area Under the Curve (AUC) for Tenofovir (TFV) During the Dosing Interval of 0 to 24 Hours (AUC0-24hr)
NCT03886701 (4) [back to overview]Doravirine Area Under the Plasma Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12)
NCT03886701 (4) [back to overview]Doravirine Maximum Concentration (Cmax)
NCT03886701 (4) [back to overview]Doravirine Oral Clearance (CL/F)
NCT03886701 (4) [back to overview]Adverse Event

Percentage of Participants With Death Due to Any Cause

(NCT00023452)
Timeframe: Baseline up to Month 35

Interventionpercentage of participants (Number)
9INH1.0
3RPT/INH0.8

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Cumulative Rate of Culture-Confirmed or Probable (Clinical) TB Disease (Regardless of Age) At 33 Months After Enrollment

Cumulative TB disease rate was defined as number of participants (regardless of age) with culture-confirmed TB disease (defined as positive culture for MTB]) or probable (clinical) TB disease (defined as objective evidence of clinical TB disease [cough, fever, night sweats, weight loss, or hemoptysis] based on history or physical exam plus radiograph, CT scan, other diagnostic tests PLUS response to antituberculosis therapy AND objective improvement of radiograph or other diagnostic tests; OR evidence of granuloma with organism positive for AFB, or caseating granulomata at autopsy or biopsy) between enrollment and the 990th Day of the Trial (33 months after enrollment, or end of the trial) per 100 participants w/33 months of follow-up and was calculated using survival analysis methods (Kaplan-Meier approach). (NCT00023452)
Timeframe: Baseline up to 33 Months

InterventionTB cases per 100 participants w/followup (Number)
9INH0.49
3RPT/INH0.24

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Cumulative Rate of Culture-Confirmed TB Disease in Participants ≥18 Years of Age AND Culture Confirmed or Probable (Clinical) TB Disease Among Participants <18 Years of Age Who Completed Study Phase Therapy Within 33 Months of Enrollment

Cumulative TB disease rate was defined as number of participants ≥18 years old with culture-confirmed TB disease (defined as positive culture for MTB) and <18 years old with probable (clinical) TB disease (defined as objective evidence of clinical TB disease [cough, fever, night sweats, weight loss, or hemoptysis] based on history or physical exam plus radiograph, CT scan, other diagnostic tests PLUS response to antituberculosis therapy AND objective improvement of radiograph or other diagnostic tests; OR evidence of granuloma with organism positive for AFB], or caseating granulomata at autopsy or biopsy) between enrollment and 33 months after enrollment (for those who completed therapy within 33 months) per 100 participants w/33 months of follow-up and was calculated using survival analysis methods (Kaplan-Meier approach). (NCT00023452)
Timeframe: Baseline up to Month 33

InterventionTB cases per 100 participants w/followup (Number)
9INH0.11
3RPT/INH0.05

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Cumulative Rate of Culture-Confirmed TB Disease in Participants ≥18 Years of Age AND Culture-Confirmed or Probable (Clinical) TB Disease in Participants <18 Years of Age at 24 Months Following Completion of Study Therapy

Cumulative TB disease rate was defined as number of participants ≥18 years old with culture-confirmed TB disease (defined as positive culture for MTB) and those <18 years old with probable (clinical) TB disease (defined as objective evidence of clinical TB disease [cough, fever, night sweats, weight loss, or hemoptysis] based on history or physical exam plus radiograph, CT scan, other diagnostic tests PLUS response to antituberculosis therapy AND objective improvement of radiograph or other diagnostic tests; OR evidence of granuloma with organism positive for AFB], or caseating granulomata at autopsy or biopsy) between enrollment and 24 months after completion of study therapy per 100 participants with up to 33 months of follow-up and was calculated using survival analysis methods (Kaplan-Meier approach). (NCT00023452)
Timeframe: Baseline up to Month 27 (3RPT/INH) or Month 33 (9INH)

InterventionTB cases per 100 participants w/followup (Number)
9INH0.37
3RPT/INH0.16

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Cumulative Rate of Culture-Confirmed TB Disease in Participants ≥18 Years of Age AND Culture-Confirmed or Probable (Clinical) TB Disease in Participants Less Than [<]18 Years of Age at 33 Months After Enrollment

Cumulative TB disease rate defined as number of participants ≥18 years old with culture-confirmed TB disease (defined as positive culture for Mycobacterium tuberculosis [MTB]) and those <18 years old with probable (clinical) TB disease (defined as objective evidence of clinical TB disease [cough, fever, night sweats, weight loss, or hemoptysis] based on history or physical exam plus radiograph, computed tomography [CT] scan, other diagnostic tests PLUS response to antituberculosis therapy AND objective improvement of radiograph or other diagnostic tests; OR evidence of granuloma with organism positive for acid-fast bacilli [AFB], or caseating granulomata at autopsy or biopsy) between enrollment and the 990th Day of the Trial (33 months after enrollment, or end of the trial) per 100 participants with (w/)33 months of follow-up calculated using survival analysis methods (Kaplan-Meier approach). (NCT00023452)
Timeframe: Baseline up to Month 33

InterventionTB cases per 100 participants w/followup (Number)
9INH0.43
3RPT/INH0.19

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Percentage of Participants Who Completed the Treatment Regimen

Completion in the 3RPT/INH arm was defined as: received 12 doses of RPT/INH within 16 weeks (12 weeks optimal). However, participants were considered to have completed therapy if at least 11 doses of RPT/INH had been received (~90%) during the 16-week time period. Completion in the 9INH arm was defined as: received 270 doses of INH within 52 weeks (39 weeks optimal). However, participants were considered to have completed therapy if at least 240 doses of INH were received (~90%) during the 52-week period. (NCT00023452)
Timeframe: Baseline up to Month 3 (3RPT/INH) or Month 9 (9INH)

Interventionpercentage of participants (Number)
9INH69.0
3RPT/INH82.1

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Percentage of Participants With Drug Discontinuation Due to Adverse Drug Reactions Associated With 3RPT/INH or 9INH

Discontinuation of study drug due to an adverse drug reaction associated with either 3RPT/INH or 9INH was defined as discontinuing treatment and/or study due to a treatment-related adverse event (AE) (considered either possibly, probably, or definitely related to the study drug by the investigator). (NCT00023452)
Timeframe: Baseline up to 60 days after the last dose of study drug (Month 5 [3RPT/INH] or Month 11 [9INH])

Interventionpercentage of participants (Number)
9INH3.8
3RPT/INH4.9

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Percentage of Participants With Drug Discontinuation for Any Reason Associated With 3RPT/INH or 9INH

Drug discontinuations for any reason associated with 3RPT/INH or 9INH included all reasons for discontinuation from study treatment, regardless of relationship to treatment. (NCT00023452)
Timeframe: Baseline up to Month 3 (3RPT/INH) or Month 9 (9INH)

Interventionpercentage of participants (Number)
9INH31.0
3RPT/INH17.9

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Percentage of Participants With Resistance to Study Medications in Isolates of MTB From Participants Who Developed Active TB Disease Within 33 Months of Enrollment

Drug-susceptibility testing (DST) was performed on isolates of MTB obtained from participants who developed signs and symptoms of active TB disease (including sputum specimens or specimens from appropriate body site for extrapulmonary TB disease). DST was performed at site's local laboratory and sent to Sponsor for confirmatory susceptibility testing. DST included all drugs currently used to treat TB disease, including pyrazinamide (PZA) and fluoroquinolones. Susceptibility was tested for other drugs at the Sponsor laboratory at the following concentrations: INH, 0.02, 1.0, and 5.0 micrograms per milliliter (µg/mL) and rifampin (RIF), 1.0 µg/mL. Isolates resistant to RIF were assumed to be resistant to RPT. (NCT00023452)
Timeframe: Baseline up to Month 33

,
Interventionpercentage of participants (Number)
INH monoresistanceRIF and PZA resistant
3RPT/INH014
9INH150

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Percentage of Patients With Grade 3 or 4 Drug Toxicities Associated With 3RPT/INH or 9INH

Drug toxicities (or AEs) were graded using Common Toxicity Criteria (CTC version 2.0, Publish Date April 30, 1999, Cancer Therapy Evaluation Program). Grade 3 and 4 drug toxicities associated with 3RPT/INH or 9INH were defined as treatment-related Grade 3 or 4 AEs (considered either possibly, probably, or definitely related to the study drug by the investigator). (NCT00023452)
Timeframe: Baseline up to 60 days after the last dose of study drug (Month 5 [3RPT/INH] or Month 11 [9INH])

,
Interventionpercentage of participants (Number)
Grade 3Grade 4
3RPT/INH2.70.4
9INH2.20.4

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To Compare, by Treatment Group, the Percentage of Patients With a Negative Sputum Culture at the End of Intensive Phase Therapy.

LJ culture conversion (NCT00728507)
Timeframe: Week 8

Interventionpercentage of participants (Number)
HPZM78.3
HRZE84.3

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Percentage of Participants With Negative Lowenstein Jensen Cultures at Week 8

(NCT00814671)
Timeframe: 8 weeks

Interventionpercentage of participants w/LJ cx con (Number)
RPT45085
RIF 60094
RPT 60096

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Pharmacokinetics of Rifapentine

area under the concentration time curve (AUC[0-24]) for rifapentine administered once daily at doses of 450 mg or 600 mg in the context of multi drug intensive phase TB treatment (NCT00814671)
Timeframe: 8 weeks

Interventionug x h/ml (Median)
Rifapentine 450 mg330
Rifapentine 600 mg435

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Time to Stable Culture Conversion on Liquid MGIT Media

Time (in days) to stable culture conversion on liquid MGIT media (NCT00814671)
Timeframe: 12 weeks

Interventiondays (Median)
RPT45050
RIF 60059
RPT 60057

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Time to Stable Culture Conversion on Solid Medium

Time to stable culture conversion (in days) on Lowenstein Jensen solid medium (NCT00814671)
Timeframe: 12 weeks

Interventiondays (Median)
RPT45037
RIF 60043
RPT 60036

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Tolerability

percentage of participants discontinuing assigned treatment (NCT00814671)
Timeframe: 10 weeks

Interventionpercentage of participants (Number)
RPT4502.0
RIF 6008.3
RPT 6002.0

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Number of Participants With Grade 2 or Higher Adverse Events Over the Course of the 26 Day Trial

Number of Participants with Grade 2 or higher adverse events over 26 days (NCT01162486)
Timeframe: 26 days

InterventionParticipants (Count of Participants)
Rifampin Control1
RPT 10
RPT 21
RPT 31
RPT 40

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Midazolam, AUC Over 12 Hours Post-dose

To compare and describe, the pharmacokinetics of single-dose midazolam alone (Day 1) versus midazolam co-administered with either steady-state rifapentine at multiple daily doses (5, 10, 15, and 20 mg/kg) or rifampin at 10 mg/kg daily (Day 15) (NCT01162486)
Timeframe: days: 1, 15

,,,,
Interventionng*h/ml (Median)
AUC 0-12 Midazolam alone (Day 1)AUC 0-12 Midazolam with RIF (Day 15)
Rifampin Control15126.9
RPT 115014.2
RPT 211410.2
RPT 320414.0
RPT 417311.7

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Pharmacokinetics (AUC of RPT Over 24 Hours Post-dose)

To determine and compare the steady-state pharmacokinetics and dose linearity of escalating daily doses of rifapentine in dose cohorts of 5 mg/kg, 10 mg/kg, 15 mg/kg and 20 mg/kg in healthy volunteers after a single dose (Day 2) or multiple doses (Day 15) (NCT01162486)
Timeframe: days: 2, 15

,,,
Intervention(mcg*h/ml) (Median)
RPT AUC, Day 2 single doseRPT AUC, Day 15 multiple dose
RPT 1128218
RPT 2242330
RPT 3363560
RPT 4403483

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Cumulative Incidence of Death Due to a Non-TB Event

Cumulative incidence function estimated nonparametrically, treating TB-related deaths as competing risks. (NCT01404312)
Timeframe: From entry to occurrence of event, up to end of follow-up 3 years after last participant enrolled (median follow-up time: 3.3 years)

,
Interventionevents per 100 participants (Number)
Cumulative incidence by 1 year post-randomizationCumulative incidence by 2 years post-randomizationCumulative incidence by 3 years post-randomizationCumulative incidence by 4 years post-randomization
INH Regimen (Arm B)0.51.01.52.0
RPT Plus INH Regimen (Arm A)0.30.40.91.6

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Cumulative Incidence of Death From Any Cause

Data table estimates for percentage who died by each time point were estimated using Kaplan-Meier at 1, 2, 3, and 4 years post-entry. (NCT01404312)
Timeframe: From entry to occurrence of event, up to end of follow-up 3 years after last participant enrolled (median follow-up time: 3.3 years)

,
Interventionevents per 100 participants (Number)
1 year post-entry2 years post-entry3 years post-entry4 years post-entry
INH Regimen (Arm B)0.631.151.622.29
RPT Plus INH Regimen (Arm A)0.350.491.052.00

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Efavirenz (EFV) Plasma Concentrations in Arm A

"Mean and standard deviation.~Week 16 samples have not yet been analyzed because the metabolite assay is being validated, and requires submission for approval by the Clinical Pharmacology Quality Assurance Program. Analysis of week 16 samples are anticipated to be available in September 2019." (NCT01404312)
Timeframe: Measured at Weeks 0, 2, 4, and 16

Interventionnanograms per mL (Mean)
Week 0Week 2Week 4
RPT Plus INH Regimen (Arm A)378738704082

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Nevirapine (NVP) Plasma Concentrations in Arm A

Mean and standard deviation (NCT01404312)
Timeframe: Measured at Weeks 0, 2, and 4

Interventionnanograms per mL (Mean)
Week0Week 2Week 4
RPT Plus INH Regimen (Arm A)757362345797

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Number of Participants With Antibiotic Resistance Among Mycobacterium Tuberculosis (MTB) Isolates in Participants Who Develop Active Tuberculosis

Among MTB-diagnosed participants who underwent drug-susceptibility testing, the number who had any resistance to a particular drug. (NCT01404312)
Timeframe: After TB diagnosis

InterventionParticipants (Count of Participants)
Rifampin72268104Rifampin72268105Isoniazid72268104Isoniazid72268105Ethambutol72268104Ethambutol72268105Pyrazinamide72268104Pyrazinamide72268105
Developed ResistanceDid not Develop Resistance
RPT Plus INH Regimen (Arm A)1
INH Regimen (Arm B)1
RPT Plus INH Regimen (Arm A)14
INH Regimen (Arm B)11
RPT Plus INH Regimen (Arm A)2
RPT Plus INH Regimen (Arm A)12
RPT Plus INH Regimen (Arm A)0
RPT Plus INH Regimen (Arm A)7
INH Regimen (Arm B)7
INH Regimen (Arm B)0
RPT Plus INH Regimen (Arm A)6
INH Regimen (Arm B)6

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TB Disease-free Survival at 12M After Study Treatment Assignment Among Participants in Control Regimen, Regimen1 (2HRZE/4HR) to Experimental Regimens, Regimen3 (2HPZM/2HPM) and Regimen2 (2HPZ/2HP) (Assessable Population)

"To evaluate the efficacy of a rifapentine-containing regimen to determine whether the single substitution of rifapentine for rifampin makes it possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis~To evaluate the efficacy of a rifapentine-containing regimen that in addition substitutes moxifloxacin for ethambutol and continues moxifloxacin during the continuation phase, to determine whether it is possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis A primary outcome status of favorable, unfavorable, or not assessable was assigned. For detailed definitions of outcomes please refer to: Dorman SE, at al. N Engl J Med. 2021 May 6;384(18):1705-1718." (NCT02410772)
Timeframe: Twelve months after treatment assignment

,,
InterventionParticipants (Count of Participants)
FavorableUnfavorable
Regimen 1 (2HRZE/4HR)65670
Regimen 2 (2HPZ/2HP)645107
Regimen 3 (2HPMZ/2HPM)66888

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Absorption (ka) of INH

"PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland).~• Estimated a single absorption rate constant (ka) for the whole population" (NCT02651259)
Timeframe: Data used in the population PK analysis included the intensive PK visit (pre-dose (t0) and 0.5, 1, 2. 4, 5, 8, 12, 24, 48, 72 hours post-dose) and sparse PK visit (1, 4, 24, 48 hours post-dose).

Interventionhr-1 (Mean)
All Cohorts1.74

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Absorption Rate Constant (ka) for Rifapentine (RPT)

"PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland).~Developed a 1 compartment PK model with transit compartments for oral absorption~Estimated the transit compartment rate constant (ktr), which is synonymous with the absorption constant (ka), for the whole population Note that the mean stated below is actually the value that is obtained from a population analysis and represents a population estimate" (NCT02651259)
Timeframe: Data used in the population PK analysis included the intensive PK visit (pre-dose (t0) and 0.5, 1, 2. 4, 5, 8, 12, 24, 48, 72 hours post-dose) and sparse PK visit (1, 4, 24, 48 hours post-dose).

Interventionhr-1 (Mean)
All Cohorts1.43

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Clearance Relative to Bioavailability (CL/F) for Rifapentine (RPT)

"PK parameters from postpartum women were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland).~Developed a 1 compartment PK model with transit compartments for oral absorption~Calculated an average CL for all post-partum individuals" (NCT02651259)
Timeframe: Data used in the population PK analysis for postpartum women included the intensive PK visit (pre-dose (t0) and 0.5, 1, 2. 4, 5, 8, 12, 24, 48, 72 hours post-dose) and sparse PK visit (1, 4, 24, 48 hours post-dose).

InterventionL/hr (Mean)
All Cohorts1.64

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Clearance Relative to Bioavailability (CL/F) for Rifapentine (RPT) for Intensive and Sparse PK

"PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland).~Developed a 1 compartment PK model with transit compartments for oral absorption~Calculated an average CL for all women in the 2nd trimester (cohort I) and all women in the 3rd trimester (cohort II)" (NCT02651259)
Timeframe: Data used in the population PK analysis included the intensive PK visit (pre-dose (t0) and 0.5, 1, 2. 4, 5, 8, 12, 24, 48, 72 hours post-dose) and sparse PK visit (1, 4, 24, 48 hours post-dose).

InterventionL/hr (Mean)
Cohort 1 (Pregnant Women Enrolled in the Second Trimester)1.4
Cohort 2 (Pregnant Women Enrolled in the Third Trimester)1.50

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Clearance Relative to Bioavailability (CLmet/F) for Desacetyl Rifapentine (Des-RPT)

"PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland).~Developed a 1 compartment PK model with transit compartments for oral absorption and a separate compartment for metabolite formation~Estimated a single des-RPT CLmet/F for the whole population Note: that the mean stated below is actually the value that is obtained from a population analysis and represents a population estimate with the relative standard error" (NCT02651259)
Timeframe: Data used in the population PK analysis included the intensive PK visit (pre-dose (t0) and 0.5, 1, 2. 4, 5, 8, 12, 24, 48, 72 hours post-dose) and sparse PK visit (1, 4, 24, 48 hours post-dose).

InterventionL/hr (Mean)
All Cohorts2.82

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Cord Blood Concentrations of Desacetyl Rifapentine (Des-RPT) Among Infants

Cord blood concentrations were summarized using using R (version 3.5.1). (NCT02651259)
Timeframe: at delivery (within 3 days of life for infants).

Interventionmcg/mL (Mean)
All Cohorts3.24

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Cord Blood Concentrations of Rifapentine (RPT) Among Infants

Cord blood concentrations were summarized using using R (version 3.5.1). (NCT02651259)
Timeframe: at delivery - (within 3 days of life for infants)

Interventionmcg/mL (Mean)
All Cohorts2.97

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Number of Infants With Active TB up to 24 Weeks of Life

Based on site-specified confirmatory TB test. If women and infants were diagnosed with active TB during study they would be referred to local care for TB management and treatment. (NCT02651259)
Timeframe: Measured from birth through participants' last study visit at 24 weeks after delivery

InterventionParticipants (Count of Participants)
Cohort 1(Infants Born to Women Enrolled in Second Trimester)0
Cohort 2 (Infants Born to Women Enrolled in Third Trimester)0

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Number of Mothers With Active TB up to 24 Weeks Postpartum

Based on site-specified confirmatory TB test. If women and infants were diagnosed with active TB during study they would be referred to local care for TB management and treatment. (NCT02651259)
Timeframe: Measured from study entry through participants' last study visit at 24 weeks after delivery

InterventionParticipants (Count of Participants)
Cohort 1 (Pregnant Women Enrolled in the Second Trimester)0
Cohort 2 (Pregnant Women Enrolled in the Third Trimester)0

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Number of Participants With Discontinuation of Study Drug Due to Intolerance (Tolerability of Study Drug Regimen - i.e., RPT, INH, and Pyridoxine)

At entry and follow-up, all lab results, sign and symptoms, and diagnoses will be recorded. Also, during follow-up grade 2 events related to pregnancy complications, hepatotoxicity, hemorrhage, or peripheral neuropathy, and all grade 3 or events that result in discontinuation of study drug regimen, and that meet criteria for EAE reporting will be further evaluated and recorded. The DAIDS Table for Grading Adult and Pediatric Adverse Events (V 2.0) and Expedited AE Manual (V 2.0) were used. (NCT02651259)
Timeframe: Measured from study entry through participants' last study visit at 24 weeks after delivery

InterventionParticipants (Count of Participants)
Cohort 1 (Pregnant Women Enrolled in the Second Trimester)0
Cohort 2 (Pregnant Women Enrolled in the Third Trimester)0

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Percentage of Participants With All AEs Leading to Permanent Discontinuation of Study Drug Regimen (i.e., RPT, INH, and Pyridoxine)

At entry and follow-up, all lab results, sign and symptoms, and diagnoses were recorded. Also, during follow-up grade 2 events related to pregnancy complications, hepatotoxicity, hemorrhage, or peripheral neuropathy, and all grade 3 or events that resulted in discontinuation of study drug regimen, and that met criteria for EAE reporting would further be evaluated and recorded. The DAIDS Table for Grading Adult and Pediatric Adverse Events (V 2.0) and Expedited AE Manual (V 2.0) were used. (NCT02651259)
Timeframe: Measured from study entry through participants' last study treatment dispensation (approximately for 12 weeks)

Interventionpercent of participants (Number)
Cohort 1 (Pregnant Women Enrolled in the Second Trimester)0
Cohort 2 (Pregnant Women Enrolled in the Third Trimester)0

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Percentage of Participants With All Grade 3 and 4 AEs

At entry and follow-up, all lab results, sign and symptoms, and diagnoses were recorded. Also, during follow-up grade 2 events related to pregnancy complications, hepatotoxicity, hemorrhage, or peripheral neuropathy, and all grade 3 or events that resulted in discontinuation of study drug regimen, and that met criteria for EAE reporting would further be evaluated and recorded. The DAIDS Table for Grading Adult and Pediatric Adverse Events (V 2.0) and Expedited AE Manual (V 2.0) were used. (NCT02651259)
Timeframe: Measured from study entry through participants' last study visit at 24 weeks after delivery

Interventionpercent of participants (Number)
Cohort 1 (Pregnant Women Enrolled in the Second Trimester)20
Cohort 2 (Pregnant Women Enrolled in the Third Trimester)16

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Percentage of Participants With All Serious AEs

At entry and follow-up, all lab results, sign and symptoms, and diagnoses were recorded. Also, during follow-up grade 2 events related to pregnancy complications, hepatotoxicity, hemorrhage, or peripheral neuropathy, and all grade 3 or events that resulted in discontinuation of study drug regimen, and that met criteria for EAE reporting would further be evaluated and recorded. The DAIDS Table for Grading Adult and Pediatric Adverse Events (V 2.0) and Expedited AE Manual (V 2.0) were used. (NCT02651259)
Timeframe: Measured from study entry through participants' last study visit at 24 weeks after delivery

Interventionpercent of participants (Number)
Cohort 1 (Pregnant Women Enrolled in the Second Trimester)8
Cohort 2 (Pregnant Women Enrolled in the Third Trimester)12

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Plasma Concentrations of Rifapentine (RPT) Among Infants

Plasma concentrations were summarized using using R (version 3.5.1). (NCT02651259)
Timeframe: at delivery - (within 3 days of life for infants).

Interventionmcg/mL (Mean)
All Cohorts2.47

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Volume of Distribution of INH

"PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland).~• Estimated a single INH Vc/F for the whole population" (NCT02651259)
Timeframe: Data used in the population PK analysis included the intensive PK visit (pre-dose (t0) and 0.5, 1, 2. 4, 5, 8, 12, 24, 48, 72 hours post-dose) and sparse PK visit (1, 4, 24, 48 hours post-dose).

InterventionL (Mean)
All Cohorts107

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Volume of Distribution Relative to Bioavailability (Vc/F) for Rifapentine (RPT)

"PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland).~Developed a 1 compartment PK model with transit compartments for oral absorption~Estimated a single RPT Vc/F for for the whole population Note: that the mean stated below is actually the value that is obtained from a population analysis and represents a population estimate with the relative standard error" (NCT02651259)
Timeframe: Data used in the population PK analysis included the intensive PK visit (pre-dose (t0) and 0.5, 1, 2. 4, 5, 8, 12, 24, 48, 72 hours post-dose) and sparse PK visit (1, 4, 24, 48 hours post-dose).

InterventionL (Mean)
All Cohorts30.1

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Area Under the Curve From 0 to 24 Hours (AUC0-24) for RPT and Area Under the Curve From 0 to 24 Hours (AUC0-24) for Des-RPT Pregnant Women in 2nd and 3rd Trimester

"PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland).~Developed a 1 compartment PK model with transit compartments for oral absorption~Obtained AUC by model-based integration" (NCT02651259)
Timeframe: Data used in the population PK analysis included the intensive PK visit (pre-dose (t0) and 0.5, 1, 2. 4, 5, 8, 12, 24, 48, 72 hours post-dose) and sparse PK visit (1, 4, 24, 48 hours post-dose).

,
Interventionhour*mg/L (Mean)
AUC (0-24) for RPTAUC (0-24) for des-RPT
Cohort 1 (Pregnant Women Enrolled in the Second Trimester)424.7158.7
Cohort 2 (Pregnant Women Enrolled in the Third Trimester)406.8153.7

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Clearance (CL/F) of INH

"PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland).~Developed a 1 compartment PK model with 2 mixtures to characterize subpopulations based on acetylation status~Estimated a separate INH CL/F based on acetylation status (fast, slow)" (NCT02651259)
Timeframe: Data used in the population PK analysis included the intensive PK visit (pre-dose (t0) and 0.5, 1, 2. 4, 5, 8, 12, 24, 48, 72 hours post-dose) and sparse PK visit (1, 4, 24, 48 hours post-dose).

InterventionL/hr (Mean)
CL/F (slow acetylators)CL/F (fast acetylators)
All Cohorts8.9832.7

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Plasma Concentrations of Desacetyl Rifapentine (Des-RPT) Among Infants

Plasma blood concentrations were summarized using using R (version 3.5.1). (NCT02651259)
Timeframe: at delivery - (within 3 days of life for infants).

Interventionmcg/mL (Mean)
All Cohorts5.31

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Maximum Concentration (Cmin) for RPT and Maximum Concentration (Cmin) for Des-RPT Pregnant Women in 2nd and 3rd Trimester

"PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland).~Developed a 1 compartment PK model with transit compartments for oral absorption~Obtained Cmin by model-based estimation" (NCT02651259)
Timeframe: Data used in the population PK analysis included the intensive PK visit (pre-dose (t0) and 0.5, 1, 2. 4, 5, 8, 12, 24, 48, 72 hours post-dose) and sparse PK visit (1, 4, 24, 48 hours post-dose).

,
Interventionmg/L (Mean)
Cmin for RPTCmin for des-RPT
Cohort 1 (Pregnant Women Enrolled in the Second Trimester)1.451.06
Cohort 2 (Pregnant Women Enrolled in the Third Trimester)1.581.20

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Maximum Concentration (Cmax) for RPT Maximum Concentration (Cmax) for Des-RPT Pregnant Women in 2nd and 3rd Trimester

"PK parameters were determined from plasma concentration-time profiles using a nonlinear mixed effects model (version 7.4; ICON PLC, Dublin, Ireland).~Developed a 1 compartment PK model with transit compartments for oral absorption~Obtained Cmax by model-based estimation" (NCT02651259)
Timeframe: Data used in the population PK analysis included the intensive PK visit (pre-dose (t0) and 0.5, 1, 2. 4, 5, 8, 12, 24, 48, 72 hours post-dose) and sparse PK visit (1, 4, 24, 48 hours post-dose).

,
Interventionmg/L (Mean)
Cmax for RPTCmax for des-RPT
Cohort 1 (Pregnant Women Enrolled in the Second Trimester)30.28.76
Cohort 2 (Pregnant Women Enrolled in the Third Trimester)28.68.50

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Plasma Area Under the Curve (AUC) for Tenofovir (TFV) During the Dosing Interval of 0 to 24 Hours (AUC0-24hr)

Plasma area under the curve (AUC) during the dosing interval of 0 to 24 hours (AUC0-24hr) on day 14, 22, and 31 of TFV was calculated using the linear-up/log-down trapezoidal rule using noncompartmental methods on Phoenix WinNonlin ® (NCT03510468)
Timeframe: 0-24 hours post dosing on days 14, 22, and 31

Interventionhr*ng/ml (Geometric Mean)
Day 14Day 22Day 31
Pharmacokinetic Study in Healthy Volunteers262.2265.3230.8

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Doravirine Area Under the Plasma Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12)

Doravirine area under the plasma-concentration time curve derived from plasma sampling during one dosing interval (NCT03886701)
Timeframe: Day 4 and 21 (Period 1 and 2): 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose

Interventionhr x ug/mL (Geometric Mean)
Period 117.3
Period 212.3

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Doravirine Maximum Concentration (Cmax)

Doravirine maximum observed concentration during the dosing interval (NCT03886701)
Timeframe: Day 4 and 21 (Period 1 and 2): 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose

Interventionug/mL (Geometric Mean)
Period 11.7
Period 21.3

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Doravirine Oral Clearance (CL/F)

Doravirine apparent oral clearance derived from plasma sampling (NCT03886701)
Timeframe: Day 4 and 21 (Period 1 and 2): 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose

InterventionL/hr (Geometric Mean)
Period 15.9
Period 28.4

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Adverse Event

Safety and tolerability (NCT03886701)
Timeframe: Days 1-24 post-dose (period 1 and 2) and 31-34 post-dose (post-study)

,
Interventionparticipants (Number)
Nausea/vomitingDysuriaFeverHeadacheChillsCatheter site pain and redness
Period 1100003
Period 2011112

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