Page last updated: 2024-12-08

fosfluconazole

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

fosfluconazole: prodrug of fluconazole [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID214356
CHEMBL ID1908301
CHEBI ID31634
SCHEMBL ID378428
MeSH IDM0467247

Synonyms (46)

Synonym
fosfluconazole
194798-83-9
prodif (tn)
fosfluconazole (jan/inn)
D01429
[2-(2,4-difluorophenyl)-1,3-bis(1,2,4-triazol-1-yl)propan-2-yl] dihydrogen phosphate
NCGC00182029-01
tox21_112934
cas-194798-83-9
dtxsid3048601 ,
dtxcid6028527
uk-292,663
fosfluconazole [inn:ban]
3jij299ewh ,
procif
unii-3jij299ewh
1-(2,4-difluorophenyl)-2-(1h-1,2,4-triazol-1-yl)-1-((1h-1,2,4-triazol-1-yl)methyl)ethyl dihydrogen phosphate
uk 292663
2,4-difluoro-alpha,alpha-bis(1h-1,2,4-triazol-1-ylmethyl)benzyl alcohol, dihydrogen phosphate (ester)
CHEMBL1908301
fluconazole dihydrogen phosphate
prodif
uk-292663
chebi:31634 ,
S11263
S6467
fosfluconazole [who-dd]
fosfluconazole [jan]
fosfluconazole [mart.]
fluconazole dihydrogen phosphate ester
1-(2,4-difluorophenyl)-2-(1h-1,2,4-triazol-1-yl)-1-[(1h-1,2,4-triazol-1-yl)methyl]ethyl dihydrogen phosphate
fosfluconazole [inn]
2,4-difluoro-.alpha.,.alpha.-bis(1h-1,2,4-triazol-1-ylmethyl)benzyl alcohol, dihydrogen phosphate (ester)
fluconazole dihydrogen phosphate ester [mi]
2-(2,4-difluorophenyl)-1,3-di(1h-1,2,4-triazol-1-yl)propan-2-yl dihydrogen phosphate
SCHEMBL378428
AKOS027322694
fosfluconazole(inn)
HY-100666
CS-6032
GHJWNRRCRIGGIO-UHFFFAOYSA-N
2-(2,4-difluorophenyl)-1,3-bis(1h-1,2,4-triazol-1-yl)-2-propyl dihydrogen phosphate
BCP09246
Q1439361
A13990
AMY38821

Research Excerpts

Overview

Fosfluconazole is a phosphate prodrug of fluconazol (FLCZ) It was developed to reduce the volume of fluid required for intravenous injection.

ExcerptReferenceRelevance
"Fosfluconazole is a phosphate prodrug of fluconazole, which was developed to reduce the volume of fluid required to administer fluconazole by intravenous injection."( Population pharmacokinetics of fluconazole after administration of fosfluconazole and fluconazole in critically ill patients.
Aoyama, T; Hayashi, H; Hirata, K; Hirata, R; Matsumoto, Y; Yamamoto, Y; Yamazaki, H, 2012
)
1.34
"Fosfluconazole is a phosphate prodrug of fluconazole (FLCZ). "( The effects of renal impairment on the pharmacokinetics and safety of fosfluconazole and fluconazole following a single intravenous bolus injection of fosfluconazole.
Layton, G; Leclerc, V; Sobue, S; Tan, K; Weil, A, 2004
)
2
"Fosfluconazole is a phosphate prodrug of fluconazole that has been developed to reduce the volume of fluid required to administer fluconazole by the intravenous route. "( [Nonclinical studies and clinical studies on fosfluconazole, a triazole antifungal agent (Prodif)].
Abe, M; Ishiko, J; Kawakami, Y; Nagino, K; Shinkai, K; Sobue, S, 2004
)
2.03
"Fosfluconazole is a phosphate pro-drug of fluconazole (FLCZ). "( The effects of hepatic impairment on the pharmacokinetics of fosfluconazole and fluconazole following a single intravenous bolus injection of fosfluconazole.
Haug-Pihale, G; Sobue, S; Tan, K, 2005
)
2.01

Toxicity

ExcerptReferenceRelevance
" The adverse events reported were mild to moderate in intensity, and there was no observed relationship with impairment group."( The effects of renal impairment on the pharmacokinetics and safety of fosfluconazole and fluconazole following a single intravenous bolus injection of fosfluconazole.
Layton, G; Leclerc, V; Sobue, S; Tan, K; Weil, A, 2004
)
0.56

Pharmacokinetics

Fosfluconazole plasma concentrations were very similar across the four groups. There were no statistically significant differences in the pharmacokinetic parameters of fosflu Conazole (except for AUC(inf)) and FLCZ between Japanese and Caucasian subjects.

ExcerptReferenceRelevance
" There were no statistically significant differences in the pharmacokinetic parameters of fosfluconazole (except for AUC(inf)) and FLCZ between Japanese and Caucasian subjects."( Comparison of the pharmacokinetics of fosfluconazole and fluconazole after single intravenous administration of fosfluconazole in healthy Japanese and Caucasian volunteers.
Hust, R; Layton, G; Shaw, L; Sobue, S; Tan, K, 2004
)
0.82
"Fosfluconazole plasma concentrations were very similar across the four groups, and there was no apparent relationship between any of the fosfluconazole pharmacokinetic parameters with increasing renal impairment."( The effects of renal impairment on the pharmacokinetics and safety of fosfluconazole and fluconazole following a single intravenous bolus injection of fosfluconazole.
Layton, G; Leclerc, V; Sobue, S; Tan, K; Weil, A, 2004
)
2
" Slightly higher mean plasma concentrations of FLCZ were observed in the impaired group than in the normal group; however, hepatic impairment had no statistically significant effect on the FLCZ pharmacokinetic parameters apart from t(max)."( The effects of hepatic impairment on the pharmacokinetics of fosfluconazole and fluconazole following a single intravenous bolus injection of fosfluconazole.
Haug-Pihale, G; Sobue, S; Tan, K, 2005
)
0.57
"Fosfluconazole was more rapidly converted to FLCZ in the hepatically impaired subjects but the FLCZ pharmacokinetic parameters (except t(max)) were not statistically significantly affected by hepatic impairment."( The effects of hepatic impairment on the pharmacokinetics of fosfluconazole and fluconazole following a single intravenous bolus injection of fosfluconazole.
Haug-Pihale, G; Sobue, S; Tan, K, 2005
)
2.01
" pharmacokinetic data on 670 drugs representing, to our knowledge, the largest publicly available set of human clinical pharmacokinetic data."( Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
Lombardo, F; Obach, RS; Waters, NJ, 2008
)
0.35
" The objective of this study was to characterize the pharmacokinetics of the antifungal fluconazole after the intravenous administration of the prodrug fosfluconazole or fluconazole in critically ill patients with serious systemic fungal infections, by population pharmacokinetic analysis using the nonmem software package."( Population pharmacokinetics of fluconazole after administration of fosfluconazole and fluconazole in critically ill patients.
Aoyama, T; Hayashi, H; Hirata, K; Hirata, R; Matsumoto, Y; Yamamoto, Y; Yamazaki, H, 2012
)
0.81
" The pharmacokinetic model of fluconazole was estimated using a one-compartment model."( Population pharmacokinetics of fluconazole after administration of fosfluconazole and fluconazole in critically ill patients.
Aoyama, T; Hayashi, H; Hirata, K; Hirata, R; Matsumoto, Y; Yamamoto, Y; Yamazaki, H, 2012
)
0.62
" The significant covariates for clearance for fluconazole (CL) and volume of distribution for fluconazole (Vd) were resulted in creatinine clearance (CLcr) and body weight (BW), respectively, in the final pharmacokinetic model equations: CL (L/h) = 0·799 × [CLcr (mL/min)/92·7](0·685) and Vd (L) = 48·1 × [BW (kg)/65](1·40) , where the interpatient variabilities in CL and Vd and the intrapatient variability were 44·8%, 79·7% and 19·8%, respectively."( Population pharmacokinetics of fluconazole after administration of fosfluconazole and fluconazole in critically ill patients.
Aoyama, T; Hayashi, H; Hirata, K; Hirata, R; Matsumoto, Y; Yamamoto, Y; Yamazaki, H, 2012
)
0.62
"The present population pharmacokinetic analysis strongly indicates that fosfluconazole (and fluconazole) dosage should be optimized in terms of CLcr in critically ill patients."( Population pharmacokinetics of fluconazole after administration of fosfluconazole and fluconazole in critically ill patients.
Aoyama, T; Hayashi, H; Hirata, K; Hirata, R; Matsumoto, Y; Yamamoto, Y; Yamazaki, H, 2012
)
0.85

Bioavailability

To assess the bioavailability of fluconazole (FLCZ) from phosphate pro-drug (fosflu Conazole) to investigate the effect of loading doses on the time to achieve FLCZ steady state plasma concentrations. To investigate the pharmacokinetics of fosfluConazole following once daily multiple bolus injection in healthy male volunteers.

ExcerptReferenceRelevance
"To investigate the bioavailability of fluconazole (FLCZ) from fosfluconazole (phosphate pro-drug of FLCZ) and to compare the pharmacokinetics of fosfluconazole and FLCZ in Japanese and Caucasian subjects."( Comparison of the pharmacokinetics of fosfluconazole and fluconazole after single intravenous administration of fosfluconazole in healthy Japanese and Caucasian volunteers.
Hust, R; Layton, G; Shaw, L; Sobue, S; Tan, K, 2004
)
0.84
"The bioavailability of FLCZ after administration of fosfluconazole was 95."( Comparison of the pharmacokinetics of fosfluconazole and fluconazole after single intravenous administration of fosfluconazole in healthy Japanese and Caucasian volunteers.
Hust, R; Layton, G; Shaw, L; Sobue, S; Tan, K, 2004
)
0.85
"To assess the bioavailability of fluconazole (FLCZ) from phosphate pro-drug (fosfluconazole), to investigate the effect of loading doses on the time to achieve FLCZ steady state plasma concentrations and on safety, and to investigate the pharmacokinetics of fosfluconazole following once daily multiple bolus injection of fosfluconazole in healthy male volunteers."( Pharmacokinetics of fosfluconazole and fluconazole following multiple intravenous administration of fosfluconazole in healthy male volunteers.
Eve, M; Layton, G; Sanderson, JB; Sobue, S; Tan, K, 2004
)
0.88
"The estimated mean (90% CI) bioavailability of FLCZ from fosfluconazole was 96."( Pharmacokinetics of fosfluconazole and fluconazole following multiple intravenous administration of fosfluconazole in healthy male volunteers.
Eve, M; Layton, G; Sanderson, JB; Sobue, S; Tan, K, 2004
)
0.89
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019
)
0.51

Dosage Studied

ExcerptRelevanceReference
" In the second study two loading doses regimen led to earlier achievement of target steady state plasma concentrations (by day 3) compared with use of one or no loading dose (towards the end of the dosing period)."( Pharmacokinetics of fosfluconazole and fluconazole following multiple intravenous administration of fosfluconazole in healthy male volunteers.
Eve, M; Layton, G; Sanderson, JB; Sobue, S; Tan, K, 2004
)
0.65
"The present population pharmacokinetic analysis strongly indicates that fosfluconazole (and fluconazole) dosage should be optimized in terms of CLcr in critically ill patients."( Population pharmacokinetics of fluconazole after administration of fosfluconazole and fluconazole in critically ill patients.
Aoyama, T; Hayashi, H; Hirata, K; Hirata, R; Matsumoto, Y; Yamamoto, Y; Yamazaki, H, 2012
)
0.85
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (1)

RoleDescription
prodrugA compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.
[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
triazolesAn azole in which the five-membered heterocyclic aromatic skeleton contains three N atoms and two C atoms.
triazole antifungal drugAny triazole antifungal agent that has been used for the treatment of fungal infections in humans or animals.
conazole antifungal drugAny conazole antifungal agent that has been used for the treatment of fungal infections in animals or humans.
[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 (1)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
AR proteinHomo sapiens (human)Potency30.10650.000221.22318,912.5098AID743036
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (9)

Assay IDTitleYearJournalArticle
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID651635Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression
AID540210Clearance in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID540212Mean residence time in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID540213Half life in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID540209Volume of distribution at steady state in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID540211Fraction unbound in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (23)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's16 (69.57)29.6817
2010's5 (21.74)24.3611
2020's2 (8.70)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 24.27

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index24.27 (24.57)
Research Supply Index3.40 (2.92)
Research Growth Index4.33 (4.65)
Search Engine Demand Index26.67 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (24.27)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials6 (26.09%)5.53%
Reviews2 (8.70%)6.00%
Case Studies7 (30.43%)4.05%
Observational0 (0.00%)0.25%
Other8 (34.78%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]