Page last updated: 2024-11-13

phenprocoumon

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Description

Phenprocoumon: Coumarin derivative that acts as a long acting oral anticoagulant. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

phenprocoumon : A hydroxycoumarin that is 4-hydroxycoumarin which is substituted at position 3 by a 1-phenylpropyl group. [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]

Cross-References

ID SourceID
PubMed CID54680692
CHEMBL ID16694
CHEMBL ID1465
CHEBI ID50438
SCHEMBL ID43031
SCHEMBL ID1651720
MeSH IDM0016532

Synonyms (106)

Synonym
4-hydroxy-3-(1-phenylpropyl)-2h-chromen-2-one
bdbm768
chembl16694 ,
2h-1-benzopyran-2-one, 4-hydroxy-3-(1-phenylpropyl)-
einecs 207-108-9
phenylpropylhydroxycumarinum
marcoumar
liquamar
falithrom
marcumar
fenprocumone [dcit]
coumarin, 3-(alpha-ethylbenzyl)-4-hydroxy-
brn 1291115
phenprocoumalol
fenprocoumona [inn-spanish]
fencumar
phenprocoumonum [inn-latin]
phenprocoumone [inn-french]
3-(1'-phenyl-propyl)-4-oxycoumarin [german]
hsdb 3248
phenprocumonum
2h-pyran-2-one, 4-hydroxy-3-[[2-(1-methylethyl)phenyl]thio]-6-(3-methylphenyl)-
phenprocoumon
ro 1-4849
4-hydroxy-3-(1-phenylpropyl)chromen-2-one
u29342
phenprocoumarole
fenprocumone
435-97-2
4-hydroxy-3-(1-phenylpropyl)-2h-1-benzopyran-2-one
D05457
liquamar (tn)
phenprocoumon (usan/inn)
OPREA1_002598
phenprocoumonum
phenprocoumone
CHEBI:50438 ,
fenprocumon
3-(1'-phenyl-propyl)-4-oxycoumarin
3-(1-phenylpropyl)-4-hydroxycoumarin
3-(alpha-ethylbenzyl)-4-hydroxycoumarin
DB00946
phenprocumone
phenprocoumarol
3-(alpha-phenylpropyl)-4-hydroxycoumarin
CHEMBL1465
bs-7565 ,
ro-1-4849
AKOS002126557
70206-44-9
phenprocoumon [usan:usp:inn:ban]
q08sio485d ,
unii-q08sio485d
fenprocoumona
phenprocoumon [mi]
5999-41-7
3-(.alpha.-phenylpropyl)-4-hydroxycoumarin
phenprocoumon [orange book]
coumarin, 3-(.alpha.-ethylbenzyl)-4-hydroxy-
phenprocoumon [usan]
phenprocoumon [inn]
phenprocoumon [who-dd]
phenprocoumon [vandf]
phenprocoumon [mart.]
(+/-)-phenprocoumon
dl-3-(.alpha.-ethylbenzyl)-4-hydroxycoumarin
phenprocoumon [hsdb]
4-hydroxy-2-oxo-3-(1-phenylpropyl)-2h-chromene
S2188
gtpl6839
smr004703040
MLS006010940
SCHEMBL43031
SCHEMBL1651720
AKOS016844146
3-(.alpha.-ethylbenzyl)-4-hydroxycoumarin
DQDAYGNAKTZFIW-UHFFFAOYSA-N
4-hydroxy-3-(1-phenylpropyl)-2h-chromen-2-one #
2-hydroxy-3-(1-phenylpropyl)-4h-chromen-4-one
FT-0698417
DTXSID5023459 ,
J-510448
3-(a-ethyl-benzyl)-4-hydroxycoumarin
phenprocoumon (marcumar)
CS-0017467
HY-A0145
Z2177958148
BCP01576
3-(1-phenylpropyl)-4-hydroxycoumarin; 4-hydroxy-2-oxo-3-(1-phenylpropyl)-2h-chromene
Q267896
NCGC00346442-02
phenprocoumon 100 microg/ml in acetonitrile
D82043
435-97-2,53621-47-9 (sodium salt)
AS-77043
EN300-219939
3-[2-[(2,3,4,5,6-2h5)phenyl]propyl]-4-hydroxy-2h-1-benzopyran-2-one
2h-1-benzopyran-2-one, 4-hydroxy-3-[(1r)-1-phenylpropyl]-
dl-3-(alpha-ethylbenzyl)-4-hydroxycoumarin
phenprocoumon (usan:usp:inn:ban)
b01aa04
fenprocoumona (inn-spanish)
phenprocoumone (inn-french)
dtxcid203459
phenprocoumonum (inn-latin)
phenprocoumon (mart.)

Research Excerpts

Overview

Phenprocoumon is an anticoagulant used for thromboembolic disorder prophylaxis metabolized mainly by CYP3A4. It is a vitamin K antagonist that is widely prescribed in Europe and Latin America. Phen procoumon appears to be a clinically useful alternative in patients carrying the CYP2C9*2 and *3 alleles.

ExcerptReferenceRelevance
"Phenprocoumon is a vitamin K antagonist that is widely prescribed in Europe and Latin America for the prophylaxis and treatment of thromboembolic events."( Bleeding Complications in a Patient After the Unexpected Interaction between Valproic Acid and Phenprocoumon.
Fiebrich, HB; Gelder, FV; Maring, JG; Smolders, EJ; Valkenburg, AJ; Wieringa, A, 2024
)
3.1
"Phenprocoumon is an anticoagulant used for thromboembolic disorder prophylaxis metabolized mainly by CYP3A4. "( PPARA gene and phenprocoumon: a new predictor of response variability.
Bandinelli, E; Botton, MR; Hutz, MH; Leiria, TL; Rohde, LE, 2015
)
2.21
"Phenprocoumon is a derivative of coumarin, used as a preventative anticoagulant and in the treatment of thromboembolisms. "( Phenprocoumon poisonings.
Hollmann, T; Riesselmann, B; Tsokos, M, 2009
)
3.24
"Phenprocoumon is a commonly used oral anticoagulant of the coumarin type, and has found extensive clinical use in the treatment of thrombophlebitis, pulmonary embolism and atrial fibrillation. "( Determination of (R)- and (S)-phenprocoumon in human plasma by enantioselective liquid chromatography/electrospray ionisation tandem mass spectrometry.
Gleiter, CH; Kahlich, R; Kammerer, B; Laufer, S; Ufer, M, 2004
)
2.05
"Phenprocoumon appears to be a clinically useful alternative in patients carrying the CYP2C9*2 and *3 alleles."( The risk of overanticoagulation in patients with cytochrome P450 CYP2C9*2 or CYP2C9*3 alleles on acenocoumarol or phenprocoumon.
De Smet, PA; Hofman, A; Kasbergen, AA; Stricker, BH; van Duijn, CM; van Schaik, RH; van Vliet, M; Visser, LE; Vulto, AG, 2004
)
1.26

Actions

ExcerptReferenceRelevance
"Phenprocoumon can cause liver damage even when the drug has been taken for prolonged periods without any problems. "( [Phenprocoumon-induced liver failure].
Cordes, A; Dahm, HH; Maier, KP; Vogt, W, 2003
)
2.67

Treatment

The phenprocoumon overdose was treated by the administration of vitamin K and PCC. Both groups were followed for 1 year after randomization.

ExcerptReferenceRelevance
"The phenprocoumon overdose was treated by the administration of vitamin K and PCC."( Massive intoxication with rivaroxaban, phenprocoumon, and diclofenac: A case report.
Eckstein, R; Herbst, L; Pfeiffer, H; Schwarze, B; Weisbach, V, 2016
)
1.18
"Phenprocoumon treatment was stopped after the first reevaluation and both groups were followed for 1 year after randomization."( Phenprocoumon for prevention of shunt occlusion after transjugular intrahepatic portosystemic stent shunt: a randomized trial.
Bruckner, T; Herrmann, S; Richter, G; Roeren, T; Sauer, P; Stiehl, A; Stremmel, W; Theilmann, L, 1996
)
2.46

Toxicity

Acenocoumarol has been proposed repeatedly as a safe alternative drug regimen for oral anticoagulation in patients who have suffered phenprocoumon-induced fulminant hepatic failure.

ExcerptReferenceRelevance
"Acenocoumarol has been proposed repeatedly as a safe alternative drug regimen for oral anticoagulation in patients who have suffered phenprocoumon-induced fulminant hepatic failure."( Acenocoumarol is not a safe alternative for anticoagulation in phenprocoumon-induced hepatic failure. Report of two cases.
Fischer, HP; Kerekes, Z; Neef, M; Sauerbruch, T; Spengler, U, 2003
)
0.76
"Perilesional sclerotherapy with foam is a safe and efficient therapy for patients with chronic venous leg ulcers even with postthrombotic syndrome and/ or ongoing anticoagulation."( Safety and efficiency of perilesional sclerotherapy in leg ulcer patients with postthrombotic syndrome and/or oral anticoagulation with phenprocoumon.
Altmeyer, P; Hermes, N; Reich, S; Stücker, M, 2006
)
0.54
"In patients receiving oral anticoagulant therapy with a target INR of 2,0-3,0 and at an intermediate risk of thromboembolic events who require interruption of oral anticoagulant therapy a half therapeutic dose of enoxaparin seems to be safe and effective for bridging."( Bridging with enoxaparin using a half-therapeutic dose regimen: safety and efficacy.
Essers, E; Gottstein, S; Klamroth, R; Landgraf, H, 2010
)
0.36
"In patients undergoing left atrial RFA, continuous periprocedural rivaroxaban use seems to be as safe as uninterrupted periprocedural phenprocoumon administration."( Safety of continuous periprocedural rivaroxaban for patients undergoing left atrial catheter ablation procedures.
Ammar, S; Buiatti, A; Deisenhofer, I; Dillier, R; Hessling, G; Hofmann, M; Kaess, B; Kathan, S; Kolb, C; Lennerz, C; Pavaci, H; Reents, T; Semmler, V, 2014
)
0.61
" Left atrial ablation procedures under continuous oral anticoagulation with apixaban are feasible and as safe as under continuous oral anticoagulation with phenprocoumon."( Comparison of safety of left atrial catheter ablation procedures for atrial arrhythmias under continuous anticoagulation with apixaban versus phenprocoumon.
Ammar, S; Bourier, F; Buiatti, A; Deisenhofer, I; Dillier, R; Grebmer, C; Hessling, G; Kaess, BM; Kolb, C; Lennerz, C; Reents, T; Semmler, V, 2015
)
0.82
" This study evaluates the total complications and the impact of novel oral anticoagulants (NOACs) compared to phenprocoumon on adverse events in the setting of PVI using CB."( The Total Incidence of Complications and the Impact of an Anticoagulation Regime on Adverse Events After Cryoballoon Ablation of Atrial Fibrillation: A Single-Center Study of 409 Patients.
Dahmen, A; Gorr, E; Hoppe, C; Horlitz, M; Keskin, K; Koektuerk, B; Schoett, M; Turan, CH; Turan, RG; Yang, A; Yorgun, H, 2016
)
0.65
"The incidence of adverse events in PVI using the second-generation CB with the periprocedural administration of NAOCs was not significantly different compared to phenprocoumon."( The Total Incidence of Complications and the Impact of an Anticoagulation Regime on Adverse Events After Cryoballoon Ablation of Atrial Fibrillation: A Single-Center Study of 409 Patients.
Dahmen, A; Gorr, E; Hoppe, C; Horlitz, M; Keskin, K; Koektuerk, B; Schoett, M; Turan, CH; Turan, RG; Yang, A; Yorgun, H, 2016
)
0.63
"VKA therapy without additional antiplatelet treatment is effective and safe in AF patients undergoing TAVI."( Feasibility and safety of vitamin K antagonist monotherapy in atrial fibrillation patients undergoing transcatheter aortic valve implantation.
Bekeredjian, R; Chorianopoulos, E; Geis, NA; Katus, HA; Kiriakou, C; Pleger, ST, 2017
)
0.46
" Uninterrupted OAC with edoxaban appeared to be as safe as uninterrupted OAC with phenprocoumon in patients who underwent LA RF ablation procedures."( Safety of Uninterrupted Periprocedural Edoxaban Versus Phenprocoumon for Patients Who Underwent Left Atrial Catheter Ablation Procedures.
Ammar-Busch, S; Bourier, F; Brkic, A; Brooks, S; Deisenhofer, I; Dillier, R; Grebmer, C; Hessling, G; Kaess, B; Koch-Büttner, K; Kolb, C; Kornmayer, M; Kottmaier, M; Lengauer, S; Lennerz, C; Pausch, H; Reents, T; Rousseva, E; Semmler, V; Telishevska, M, 2018
)
0.95

Pharmacokinetics

Pantoprazole does not interact with the anticoagulant phenprocoumon. The pharmacokinetic characteristics AUC0-24h and Cmax of S(-)- and R(+)-phenprocouMon were also investigated using equivalence criteria.

ExcerptReferenceRelevance
" The results show that S(-) phenprocoumon is more potent anticoagulant than R(+) phenprocoumon and that the pharmacokinetic differences between the enantiomers are due mainly to differences in their distribution."( The enantiomers of phenprocoumon: pharmacodynamic and pharmacokinetic studies.
Gilfrich, HJ; Groth, U; Jähnchen, E; Martini, A; Meinertz, T, 1976
)
0.88
"According to a pharmacokinetic model, the adjustment of a phenprocoumon (PPC) standard dosage based on experimentally determined means values of the parameters volume of distribution and biological half-life will yield in more than 50% of the individuals the desired plasma PPC concentration."( Adjustment of phenprocoumon dosage utilizing a pharmacokinetic model.
Barthel, W; Böhm, K; Vogel, G, 1988
)
0.88
" The usual pharmacokinetic parameters were calculated from the concentrations measured."( The effect of wheat bran on the pharmacokinetics of phenprocoumon in normal volunteers.
Kitteringham, NR; Mineshita, S; Ohnhaus, EE, 1985
)
0.52
"The model presented here is based on a phenprocoumon (PPC) standard dose calculated per kg body weight by adapting it to experimentally obtained mean values of biological half-life (t1/2) and relative volume of distribution (Vrel) of PPC taken from the literature."( A pharmacokinetic model of the adjustment of phenprocoumon (Falithrom) dosage.
Barthel, W, 1984
)
0.8
"In 23 female and male healthy volunteers the pharmacokinetic behaviour of [3H]phenprocoumon and [3H]phytomenadion was investigated."( Interaction between phenprocoumon and phytomenadion: a pharmacokinetic investigation in healthy volunteers.
Haustein, KO, 1984
)
0.82
"The possibility of a pharmacokinetic interaction between carvedilol and digitoxin (Study I) or phenprocoumon (Study II) has been evaluated in groups of 12 healthy volunteers."( Lack of a pharmacokinetic interaction between carvedilol and digitoxin or phenprocoumon.
Brei, R; Caspary, S; Harder, S; Merz, PG, 1993
)
0.74
"The pharmacodynamic properties of meloxicam, a new nonsteroidal antiinflammatory drug (NSAID), that go beyond those typical of an NSAID were examined."( General pharmacology of meloxicam--Part II: Effects on blood pressure, blood flow, heart rate, ECG, respiratory minute volume and interactions with paracetamol, pirenzepine, chlorthalidone, phenprocoumon and tolbutamide.
Engelhardt, G; Homma, D; Schlegel, K; Schnitzler, C; Utzmann, R, 1996
)
0.48
" As a pharmacodynamic parameter, the prothrombin time ratio was determined on days 9 and 10 (reference value) and on days 14 and 15 (test value), and the ratio test/reference was evaluated according to equivalence criteria."( Lack of pharmacodynamic and pharmacokinetic interaction between pantoprazole and phenprocoumon in man.
Birkel, M; Bliesath, H; Ehrlich, A; Fuder, H; Hartmann, M; Huber, R; Lücker, PW; Steinijans, VW; Timmer, W; Wieckhorst, G; Wurst, W, 1996
)
0.52
" The pharmacokinetic characteristics AUC0-24h and Cmax of S(-)- and R(+)-phenprocoumon were also investigated using equivalence criteria."( Lack of pharmacodynamic and pharmacokinetic interaction between pantoprazole and phenprocoumon in man.
Birkel, M; Bliesath, H; Ehrlich, A; Fuder, H; Hartmann, M; Huber, R; Lücker, PW; Steinijans, VW; Timmer, W; Wieckhorst, G; Wurst, W, 1996
)
0.75
"Pantoprazole does not interact with the anticoagulant phenprocoumon on a pharmacodynamic or pharmacokinetic level."( Lack of pharmacodynamic and pharmacokinetic interaction between pantoprazole and phenprocoumon in man.
Birkel, M; Bliesath, H; Ehrlich, A; Fuder, H; Hartmann, M; Huber, R; Lücker, PW; Steinijans, VW; Timmer, W; Wieckhorst, G; Wurst, W, 1996
)
0.77
" For this reason, the study of the pharmacokinetic parameters of phenprocoumon (PPC), considering its influence on blood clotting factors, is of high interest."( Pharmacokinetic and pharmacodynamic properties of oral anticoagulants, especially phenprocoumon.
Haustein, KO, 1999
)
0.77
" An approach to predict pharmacokinetic interactions of lornoxicam from in vitro inhibition data was developed."( Prediction of pharmacokinetic drug/drug interactions from In vitro data: interactions of the nonsteroidal anti-inflammatory drug lornoxicam with oral anticoagulants.
Kohl, C; Steinkellner, M, 2000
)
0.31
" No significant effect of the CYP2C9 variants *2 and *3 on R-phenprocoumon pharmacokinetic parameters was detected, but S-phenprocoumon clearance tended to decrease with increasing number of CYP2C9*2 and *3 alleles."( Effects of CYP2C9 polymorphisms on the pharmacokinetics of R- and S-phenprocoumon in healthy volunteers.
Brockmöller, J; Gleiter, CH; Kahlich, R; Kammerer, B; Kirchheiner, J; Meisel, C; Rane, A; Roots, I; Schwab, M; Ufer, M; Walter, EC, 2004
)
0.8
" The pharmacokinetics are, however, substantially less dependent on CYP2C9 activity or genotype than for other CYP2C9-metabolised VKAs, and pharmacokinetic differences for the enantiomers are only minor."( Stereospecific pharmacokinetic characterisation of phenprocoumon metabolites, and mass-spectrometric identification of two novel metabolites in human plasma and liver microsomes.
Gleiter, CH; Kahlich, R; Kammerer, B; Laufer, S; Schenkel, A; Ufer, M, 2005
)
0.58
" These large dose response variations are markedly influenced by pharmacokinetic aspects that are determined by genetic, environmental and possibly other yet unknown factors."( Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol.
Ufer, M, 2005
)
0.57
"The model provides a deeper insight in the separate pharmacokinetic and pharmacodynamic parts of phenprocoumon action."( Quantifying the effect of covariates on concentrations and effects of steady-state phenprocoumon using a population pharmacokinetic/pharmacodynamic model.
Abduljalil, K; Fuhr, U; Gleiter, C; Harenberg, J; Kohl, V; Lazar, S; Mörike, K; Natanzon, M; Schwab, M; Steffens, B; Stingl, J; Tomalik-Scharte, D; Wu, W; Zadoyan, G, 2013
)
0.83
" POCT for aPTT is sensitive to increased concentrations of dabigatran, whereas the PT-POCT assessed with test systems such as the GEM PCL Plus may be helpful to measure the pharmacodynamic anticoagulant effects of rivaroxaban in emergency clinical situations."( Point-of-care coagulation testing for assessment of the pharmacodynamic anticoagulant effect of direct oral anticoagulant.
Herrmann, E; Herth, N; Kasper, A; Lindhoff-Last, E; Linnemann, B; Mani, H; Pfeilschifter, W; Schuettfort, G; Weil, Y; Wendt, T, 2014
)
0.4

Compound-Compound Interactions

ExcerptReferenceRelevance
"In a prospective randomized trial in 42 patients undergoing coronary artery bypass surgery, we analyzed the long term platelet inhibiting effects of 50 mg acetylsalicylic acid (ASA) by itself and in combination with dipyridamole (2 x 200 mg), in comparison with phenprocoumon."( [Long term effects of 50 mg acetylsalicylic acid alone and in combination with dipyridamole on platelet function after coronary bypass surgery].
Hoffmann, MW; Rauhöft, C; Terres, W, 1998
)
0.48
"We present a database of prescription drugs and international normalized ratio (INR) data and the applied methodology for its use to assess drug-drug interactions with vitamin K antagonists (VKAs)."( Pharmacoepidemiological assessment of drug interactions with vitamin K antagonists.
dePont Christensen, R; Gagne, JJ; Hallas, J; Larsen, TB; Pottegård, A; Wang, SV, 2014
)
0.4

Bioavailability

The bioavailability (Cmax, tmax, AUC) of digitoxin and phenprocoumon were assessed after a single dose. The most important factors are the susceptibility of vitamin K antagonists to nutrition or metabolic irregularities. The influence of liquorice on the function of isoenzymes of the cytochrome P450 family may lead to reduced bioavailability.

ExcerptReferenceRelevance
" The systemic bioavailability of oral phenprocoumon was 97."( [The treatment basis for anticoagulants in horses].
Sinn, D; Wintzer, HJ, 1990
)
0.55
" Following the ingestion of wheat bran, a decreased absorption rate for phenprocoumon but no decrease in overall bioavailability was observed."( The effect of wheat bran on the pharmacokinetics of phenprocoumon in normal volunteers.
Kitteringham, NR; Mineshita, S; Ohnhaus, EE, 1985
)
0.75
"The low oral bioavailability and rapid biliary excretion of peptide-derived HIV protease inhibitors have limited their utility as potential therapeutic agents."( Structure-based design of novel HIV protease inhibitors: sulfonamide-containing 4-hydroxycoumarins and 4-hydroxy-2-pyrones as potent non-peptidic inhibitors.
Chong, KT; Dolak, LA; Hinshaw, RR; Horng, MM; Janakiraman, MN; Lynn, JC; Strohbach, JW; Thaisrivongs, S; Tomich, PK; Turner, SR; Watenpaugh, KD, 1996
)
0.29
" In a model-based analysis, an increase of (S)-phenprocoumon and (R)-phenprocoumon bioavailability of 14% [95% CI (9%, 19%)] and 6% (2%, 10%) and a decrease of their clearances by 15% (8%, 21%) and 6% (0%, 13%) was obtained."( Opposite effects of lornoxicam co-administration on phenprocoumon pharmacokinetics and pharmacodynamics.
Fattinger, KE; Masche, UP; Meier, PJ; Rentsch, KM; von Felten, A, 1999
)
0.81
" The literature shows that the bioavailability from solutions might be higher than that from tablets, possibly resulting in different effects."( Vitamin K1 in oral solution or tablets: a crossover trial and two randomized controlled trials to compare effects.
Gebuis, EP; Groeneveld, JJ; le Cessie, S; Lijfering, WM; Rosendaal, FR; van der Horst, FA; van der Meer, FJ; van Rein, N, 2014
)
0.4
"To compare the bioavailability and effect on the International Normalized Ratio (INR) of 5-mg VK1 tablets and solution in three randomized clinical trials."( Vitamin K1 in oral solution or tablets: a crossover trial and two randomized controlled trials to compare effects.
Gebuis, EP; Groeneveld, JJ; le Cessie, S; Lijfering, WM; Rosendaal, FR; van der Horst, FA; van der Meer, FJ; van Rein, N, 2014
)
0.4
"The bioavailability was determined in a crossover trial with 25 healthy volunteers."( Vitamin K1 in oral solution or tablets: a crossover trial and two randomized controlled trials to compare effects.
Gebuis, EP; Groeneveld, JJ; le Cessie, S; Lijfering, WM; Rosendaal, FR; van der Horst, FA; van der Meer, FJ; van Rein, N, 2014
)
0.4
" In this context, the most important factors are the susceptibility of vitamin K antagonists to nutrition or metabolic irregularities, the influence of liquorice on the function of isoenzymes of the cytochrome P450 family that may lead to reduced bioavailability of phenprocoumon, and the influence of liquorice on peroxisome proliferator-activated receptor alpha transactivation."( The influence of excessive consumption of liquorice on phenprocoumon (Marcumar®): a case report.
Botzenhardt, S; Kunz, L; Roemer, HC, 2021
)
1.05

Dosage Studied

Phenprocoumon had a lower dosage requirement in carriers of CYP2C9*2 or *3. The role of these genetic variants on dosing and the safe use of phenprocouMon is less well investigated.

ExcerptRelevanceReference
" Phenobarbital at plasma concentrations achieved by usual therapeutical dosage schedules of the drug does not interfere with the protein binding of phenprocoumon as could be shown by equilibrium dialysis."( [Elimination kinetics of phenprocoumon (Marcumar) in liver cirrhosis and after premedication with phenobarbital].
Glogner, P; Heni, N; Lehnhardt, G, 1976
)
0.76
" Continuous incorrect dosage resulted in KF change, equilibrating at a new level after about four weeks at -0."( [Analysis of phenprocoumon dose regulation based on measurement of coagulation factors II, VII and X].
Heaf, JG, 1992
)
0.65
" The risk of therapy with acetyl salicylic acid (ASS) in low dosage is significantly smaller."( [Experiences from general practice: use of acetylsalicylic acid and anticoagulants in patients following acute myocardial infarct].
Dahn, G; Kothe, K, 1990
)
0.28
"According to a pharmacokinetic model, the adjustment of a phenprocoumon (PPC) standard dosage based on experimentally determined means values of the parameters volume of distribution and biological half-life will yield in more than 50% of the individuals the desired plasma PPC concentration."( Adjustment of phenprocoumon dosage utilizing a pharmacokinetic model.
Barthel, W; Böhm, K; Vogel, G, 1988
)
0.88
"The dose-response relationship of the Vitamine-K-antagonist Phenprocoumon (Marcumar) was studied in a group of 11 children and 10 adults receiving anticoagulation postoperatively after mechanical valve replacement."( [Anticoagulation with phenprocoumon in early childhood: dosage, complications, effectiveness].
Engelhardt, W; Mühler, E; von Bernuth, G,
)
0.69
" Afterwards the dosage regimens were kept unchanged until day 40 when 60 mg oral vitamin K1 were administered."( Lack of effect of acitretin on the hypothrombinemic action of phenprocoumon in healthy volunteers.
Hartmann, D; Mosberg, H; Weber, W, 1989
)
0.52
" As the phenprocoumon dosage was kept unchanged during the double-blind phase, the results indicate that ramipril does not interfere with the vitamin K-dependent cascade."( Absence of interaction between ramipril, a new ACE-inhibitor, and phenprocoumon, an anticoagulant agent.
Grötsch, H; Malerczyk, V; Verho, M; Zenbil, I, 1989
)
0.95
"The blood coagulating factors II and VII and prothrombin times (Thrombotest) were followed during a dosage interval (= 24 h) in patients on acenocoumarol (n = 6) and on phenprocoumon (n = 6) therapy."( 4-Hydroxycoumarin oral anticoagulants: pharmacokinetics-response relationship.
Hamulyák, K; Thijssen, HH; Willigers, H, 1988
)
0.47
" A 7-fold difference in the dosing rate (10-70 micrograms/kg/day) was required to maintain the prothrombin complex activity at 11-30% of normal."( Factors responsible for interindividual differences in the dose requirement of phenprocoumon.
Althen, H; Jähnchen, E; Meinertz, T; Oie, S; Trenk, D, 1987
)
0.5
" Apparent failures of this treatment may be caused by insufficient information on the part of either the physician or the patient himself, poor standardization of laboratory tests and/or inadequate dosage of vitamin K antagonists."( [How can we improve long-term anticoagulation?].
Beck, EA, 1985
)
0.27
" Application of the basic principles of the present model to clinical practice would allow to further optimize and individualize the adjustment of multiple dosing regimen of the oral anticoagulant PPC."( A pharmacokinetic model of the adjustment of phenprocoumon (Falithrom) dosage.
Barthel, W, 1984
)
0.53
" Co-administration of metoprolol, but not atenolol, increased mean plasma phenprocoumon concentrations 4 and 6 h after dosing and was caused by a decrease in the apparent volume of distribution."( Pharmacokinetic and pharmacodynamic interactions between phenprocoumon and atenolol or metoprolol.
Kirch, W; Kitteringham, NR; Lögering, HJ; Mutschler, E; Ohnhaus, EE; Paar, D; Spahn, H, 1984
)
0.74
" After the antibiotics were discontinued, the original dosage of phenprocoumon was needed again."( [Possible potentiation of phenprocoumon by clarithromycin and roxithromycin].
Egberts, AC; Heere, FJ; Lastdrager, CJ; Meyboom, RH, 1996
)
0.83
" The treatment with prothrombin complex concentrates requires a strict risk-benefit estimation and laboratory monitoring is recommended to optimize dosage adjustment."( The overdosed patient and bleedings with oral anticoagulation.
Heinrich, W; Krischek, B; Mörsdorf, S; Pindur, G; Schenk, JF; Wenzel, E, 1999
)
0.3
" For practical reasons, despite lack of established effectiveness in Trousseau's syndrome, therapy was switched to low-molecular-weight heparin (LMWH, nadroparine) in therapeutic dosage of 100 IU/kg body wt."( [Recurrent thromboembolisms despite oral anticoagulation in a 76-year-old patient--Trousseau syndrome].
Demarmels Biasiutti, F; Züger, M, 1999
)
0.3
" The dosage scheme was subsequently tested in a pilot study including 35 patients."( Evaluation of a simple dosage scheme for transition from phenprocoumon to warfarin in oral anticoagulation.
Brandslund, I; Dahler-Eriksen, BS; Dahler-Eriksen, K; Kristiansen, C; Larsen, TB; Lassen, JF, 2000
)
0.55
" Any interfering co-medication can pose a challenge to establishing a stable anticoagulant dosage regimen and thus present a serious risk for the patient."( Drug interaction: omeprazole and phenprocoumon.
Enderle, C; Grass, U; Müller, W, 2001
)
0.59
"A recent case control study suggests that paracetamol at a dosage above 1300 mg/day increases the anticoagulant effects of warfarin."( No clinically relevant drug interaction between paracetamol and phenprocoumon based on a pharmacoepidemiological cohort study in medical inpatients.
Braunschweig, S; Fattinger, K; Frisullo, R; Masche, U; Meier, PJ; Roos, M, 2002
)
0.55
"These results suggest that paracetamol co-administration at a dosage of 2000-2500 mg/day for 3 days has no clinically relevant effects on the anticoagulant effects of phenprocoumon."( No clinically relevant drug interaction between paracetamol and phenprocoumon based on a pharmacoepidemiological cohort study in medical inpatients.
Braunschweig, S; Fattinger, K; Frisullo, R; Masche, U; Meier, PJ; Roos, M, 2002
)
0.75
" The aim of our study was to find proper dosage regimens of phenprocoumon and warfarin allowing initiation of oral anticoagulant treatment in a short time."( [Initiation of oral anticoagulant treatment: comparison between different dosage regimens of warfarin and phenprocoumon].
Bernardo, A; Heidt, M; Kemkes-Matthes, B; Matzdorff, A; Winkler, L, 2002
)
0.77
"125 patients treated as inpatients for atrial fibrillation or -flutter received the LMWH Fragmin (dalteparin 2 x 100 anti-Xa units/kg, maximum dosage 2 x 10,000 anti-Xa units subcutaneously)."( Anticoagulation with the low-molecular-weight heparin dalteparin (Fragmin) in atrial fibrillation and TEE-guided cardioversion.
Bechtold, H; Fung, S; Gunzenhauser, D; Janssen, D; Sawitzki, H, 2003
)
0.32
" This retrospective cohort study compiled data during a three-year period from a computerised dosing and management system."( Comparison of control and stability of oral anticoagulant therapy using acenocoumarol versus phenprocoumon.
Antheunissen-Anneveld, I; Breukink-Engbers, WG; de Vries-Goldschmeding, H; Fihn, SD; Gadisseur, AA; Geven-Boere, LM; Harderman, D; Pasterkamp, E; Rosendaal, FR; Smink, M; van der Meer, FJ; van Meegen, E; van't Hoff, AR, 2003
)
0.54
" Argatroban and melagatran delivered biphasic dose-response curves."( Effects of lepirudin, argatroban and melagatran and additional influence of phenprocoumon on ecarin clotting time.
Fenyvesi, T; Harenberg, J; Jörg, I; Weiss, C, 2003
)
0.55
"0 microg/kg/min ARG (days 1, 3, 4 and 5) before initiation of either PC or AC (day 1) and during continued VKA dosing (target INR 2-3)."( Transition from argatroban to oral anticoagulation with phenprocoumon or acenocoumarol: effects on prothrombin time, activated partial thromboplastin time, and Ecarin Clotting Time.
Breddin, HK; Graff, J; Harder, S; Klinkhardt, U; Osakabe, M; von Hentig, N; Walenga, JM; Watanabe, H, 2004
)
0.57
" Carriers of the CYP2C9*2 or *3 allele needed a significantly lower phenprocoumon dosage compared with homozygous CYP2C9*1/*1 subjects."( Effects of cytochrome P450 2C9 polymorphisms on phenprocoumon anticoagulation status.
Conemans, J; de Boer, A; Hermans, M; Meijerman, I; Oosterhof, M; Schalekamp, T; van Der Meer, FJ; van Meegen, E, 2004
)
0.81
" Similar to warfarin and acenocoumarol, phenprocoumon had a lower dosage requirement in carriers of CYP2C9*2 or *3 compared with that in CYP2C9 wild-type subjects."( Effects of cytochrome P450 2C9 polymorphisms on phenprocoumon anticoagulation status.
Conemans, J; de Boer, A; Hermans, M; Meijerman, I; Oosterhof, M; Schalekamp, T; van Der Meer, FJ; van Meegen, E, 2004
)
0.85
" These algorithms are usually based on an empiric relationship between dosage and International Normalized Ratio and do not quantify the delaying effect of the drug's pharmacokinetics or the effect of alternating doses that are used to approximate a certain average dosage."( A model-based algorithm for the monitoring of long-term anticoagulation therapy.
Kruithof, CJ; Pasterkamp, E; Rosendaal, FR; Van der Meer, FJ; Vanderschoot, JP, 2005
)
0.33
" In contrast, uniform recommendations regarding the indication, route of administration, and dosing of thrombolytic therapy in children are not available."( Thrombolysis of venous and arterial thrombosis by catheter-directed low-dose infusion of tissue plasminogen activator in children.
Albisetti, M; Berger, F; Cannizzaro, V; Knirsch, W; Kretschmar, O; Saurenmann, R, 2005
)
0.33
" The use of vitamin K antagonists is complicated by a narrow therapeutic index and an unpredictable dose-response relationship, giving rise to frequent bleeding complications or insufficient anticoagulation."( Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol.
Ufer, M, 2005
)
0.57
"001] and the lower the required dosage until the therapeutic range was achieved [BMI <22 (n=31), 23."( Obesity is associated with a slower response to initial phenprocoumon therapy whereas CYP2C9 genotypes are not.
Hoffmann, R; Langebartels, G; Mevissen, V; Meyer zu Schwabedissen, C; Ortlepp, JR; Rau, T; Schmitz, F; Woodruff, S; Zerres, K, 2006
)
0.58
" The desired level of anticoagulation was achieved with a high dosage of phenprocoumon (18-21 mg daily)."( [Partial resistance to acenocoumarol and phenprocoumon caused by enzyme polymorphism].
Touw, DJ; van Meegen, E; Veldkamp, RF; Wilms, EB, 2006
)
0.83
" The dosage of enoxaparin was 1 mg/kg bodyweight twice daily in treatment phase I followed by 40 mg twice daily with a bodyweight <65 kg or 60 mg twice daily with a BW > or =65 kg in treatment phase II."( Economic evaluation of enoxaparin for anticoagulation in early cardioversion of persisting nonvalvular atrial fibrillation: a statutory health insurance perspective from Germany.
Brecht, JG; Huppertz, E; Lehmacher, W; Nixdorff, U; Schädlich, PK; Schmidt-Lucke, C; Stellbrink, C, 2007
)
0.34
" Mean phenprocoumon dosage per week to achieve therapeutic anticoagulation was lower (higher) in patients with than without the VKORC1 polymorphism -1639G > A (3730G > A) or the CYP2C9 polymorphisms."( Dependency of phenprocoumon dosage on polymorphisms in the VKORC1 and CYP2C9 genes.
Dossenbach-Glaninger, A; Finsterer, J; Krugluger, W; Qazim, B; Stöllberger, C, 2009
)
1.19
"Though VKORC1 and CYP2C9 polymorphisms influence the phenprocoumon dosage necessary to achieve therapeutic anticoagulation, anticoagulation is therapeutic if carefully monitored."( Dependency of phenprocoumon dosage on polymorphisms in the VKORC1 and CYP2C9 genes.
Dossenbach-Glaninger, A; Finsterer, J; Krugluger, W; Qazim, B; Stöllberger, C, 2009
)
0.96
" The management of oral anticoagulation is challenging because of a large variability in the dose-response relationship, which is in part caused by genetic polymorphisms."( Pharmacogenetics of oral anticoagulants: a basis for dose individualization.
Fuhr, U; Kirchheiner, J; Lazar, A; Stehle, S, 2008
)
0.35
" Several warfarin dosing algorithms have been constructed, adapted on CYP2C9 and VKORC1 genotypes and clinical factors, to predict the best dose for each patient."( Evidence for a pharmacogenetic adapted dose of oral anticoagulant in routine medical practice.
Becquemont, L, 2008
)
0.35
"To meet growing demand for oral anticoagulation worldwide there has been increased dependence on computer-assistance in dosage although the safety and effectiveness of any of the individual computer-assisted dosage programs has not previously been established."( A multicentre randomised clinical endpoint study of PARMA 5 computer-assisted oral anticoagulant dosage.
Ibrahim, S; Jespersen, J; Keown, M; Lowe, G; Moia, M; Palareti, G; Poller, L; Roberts, C; Tripodi, A; Turpie, AG; van den Besselaar, AM; van der Meer, FJ, 2008
)
0.35
" The dosage was monitored and adjusted according to the prothrombin time, which was initially measured every week, and later maximally biweekly."( [Aorto-iliac thrombosis in a gelding: treatment with the anticoagulant Phenprocoumon (Marcoumar)].
Cohausz, O; Scharf, G; Trachsel, D; Wehrli Eser, M, 2008
)
0.58
" Consecutive patients receiving enoxaparin at a dosage of 1 mg/kg body weight/12 hours for temporary interruption of phenprocoumon were prospectively enrolled to the study."( How useful is determination of anti-factor Xa activity to guide bridging therapy with enoxaparin? A pilot study.
Hammerstingl, C; Omran, H; Poetzsch, B; Tripp, C, 2009
)
0.56
" Whereas the impacts of the cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) polymorphisms on warfarin dosing are clearly established, the role of these genetic variants on dosing and the safe use of phenprocoumon are less well investigated and, to a certain degree, controversial."( Pharmacogenetic characteristics of patients with complicated phenprocoumon dosing.
Eschenhagen, T; Grosch, A; Lestin, HG; Rau, T; Werner, D; Werner, U; Wuerfel, A, 2009
)
0.78
" A feasible tool to guide coumarin dosing and thereby safely shortening time in hospital is required."( Pharmacogenetic testing for guiding de novo phenprocoumon therapy in stroke patients.
Arnold, ML; Di Mascio, MT; Grond-Ginsbach, C; Kloss, M; Lichy, C; Ringleb, P; Veltkamp, R, 2009
)
0.61
" To date, several pharmacogenetic-guided dosing algorithms for coumarin derivatives, predominately for warfarin, have been developed."( Genotype-guided dosing of coumarin derivatives: the European pharmacogenetics of anticoagulant therapy (EU-PACT) trial design.
Barallon, R; Briz, M; Daly, AK; de Boer, A; Haschke-Becher, E; Kamali, F; Kirchheiner, J; Maitland van der Zee, AH; Manolopoulos, VG; Pirmohamed, M; Redekop, WK; Rosendaal, FR; van Schie, RM; Verhoef, TI; Wadelius, MI, 2009
)
0.35
" In phase 2, stepwise OAC reversal was performed with PCC using a predetermined dosing schedule."( Point-of-care reversal treatment in phenprocoumon-related intracerebral hemorrhage.
Hacke, W; Herweh, C; Hug, A; Jenetzky, E; Rizos, T; Steiner, T; Veltkamp, R, 2010
)
0.64
" Polymorphisms in cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase genes (VKORC1) have been shown to affect VKA dosing in adults."( In pediatric patients, age has more impact on dosing of vitamin K antagonists than VKORC1 or CYP2C9 genotypes.
Dietrich, K; Eldin, NS; Geisen, C; Mitchell, LG; Nowak-Göttl, U; Schaffranek, D; Yasui, Y, 2010
)
0.36
" Up to now, the dosage is often based on the visual inspection of previous INR measurements, average weekly doses, and the INR target range."( Computer-aided dosage in oral anticoagulation therapy using phenprocoumon. Problems and approaches.
Cromme, L; Gäbler, F; Salzwedel, A; Taborski, U; Völler, H, 2010
)
0.6
"Genome-wide association studies (GWAS) on warfarin and acenocoumarol showed that interindividual dosage variation is mainly associated with single nucleotide polymorphisms (SNPs) in VKORC1 and to a lesser extent in CYP2C9 and CYP4F2."( Dependency of phenprocoumon dosage on polymorphisms in the VKORC1, CYP2C9, and CYP4F2 genes.
Buhre, PN; De Smet, PA; Eijgelsheim, M; Hofman, A; Stricker, BH; Teichert, M; Uitterlinden, AG; Visser, LE, 2011
)
0.73
"Within our study population (N=244), VKORC1, CYP2C9, CYP4F2 genotypes together explained 46% of phenprocoumon maintenance dosage variation."( Dependency of phenprocoumon dosage on polymorphisms in the VKORC1, CYP2C9, and CYP4F2 genes.
Buhre, PN; De Smet, PA; Eijgelsheim, M; Hofman, A; Stricker, BH; Teichert, M; Uitterlinden, AG; Visser, LE, 2011
)
0.95
"Similar to earlier findings with warfarin and acenocoumarol, phenprocoumon maintenance dosage depended on polymorphisms in the VKORC1 gene."( Dependency of phenprocoumon dosage on polymorphisms in the VKORC1, CYP2C9, and CYP4F2 genes.
Buhre, PN; De Smet, PA; Eijgelsheim, M; Hofman, A; Stricker, BH; Teichert, M; Uitterlinden, AG; Visser, LE, 2011
)
0.97
"In this observational, pilot study, the efficacy and feasibility of the fixed dose strategy compared to the variable dosing regimen, is investigated."( Fixed versus variable dose of prothrombin complex concentrate for counteracting vitamin K antagonist therapy.
Huisman, W; Khorsand, N; Meijer, K; Muller, M; Overdiek, JW; van Hest, RM; Veeger, NJ, 2011
)
0.37
" The investigated SNPs in CYP4F2, CALU, EPHX1, GGCX, F7, and PROC did not improve the predictive value of a pharmacogenetic-based dosing equation for phenprocoumon."( Prediction of phenprocoumon maintenance dose and phenprocoumon plasma concentration by genetic and non-genetic parameters.
Geisen, C; Lindhoff-Last, E; Luxembourg, B; Marinova, M; Oldenburg, J; Seifried, E; Sittinger, K; Toennes, SW; von Ahsen, N; Watzka, M, 2011
)
0.93
" Single nucleotide polymorphisms relevant to coumarin derivative dosing on the CYP2C9 and VKORC1 genes were determined."( Loading and maintenance dose algorithms for phenprocoumon and acenocoumarol using patient characteristics and pharmacogenetic data.
de Boer, A; le Cessie, S; Maitland-van der Zee, AH; Rosendaal, FR; Schalekamp, T; van der Meer, FJ; van Meegen, E; van Schie, RM; Verhoef, TI; Wessels, JA, 2011
)
0.63
" Patient charts were reviewed for a predefined set of possible causes: Drug-drug interactions, alcohol abuse, disease, start-up or recent change in dosage and dosage errors."( Excessive anticoagulation with warfarin or phenprocoumon may have multiple causes.
Hallas, J; Holck, LH; Madsen, H; Meegaard, PM; Pottegård, A, 2012
)
0.64
"Inpatients with new-onset anticoagulation were randomised to one of two computer assisted dosing algorithms, or to a control arm."( Randomised trial of a clinical dosing algorithm to start anticoagulation with phenprocoumon.
Caduff Good, A; Geisen, C; Henz, S; Krähenbühl, S; Nobel, D, 2013
)
0.62
"Both algorithms allow safe initial dosing of phenprocoumon but they are not superior to anticoagulation by trained physicians."( Randomised trial of a clinical dosing algorithm to start anticoagulation with phenprocoumon.
Caduff Good, A; Geisen, C; Henz, S; Krähenbühl, S; Nobel, D, 2013
)
0.88
"VKORC polymorphism affects PC dosage and anticoagulation-related complication rates in mechanical heart valve recipients."( Mechanical heart valve recipients: anticoagulation in patients with genetic variations of phenprocoumon metabolism.
Beyersdorf, F; Blanke, P; Brehm, K; Geissler, HJ; Heilmann, C; Schack, J, 2013
)
0.61
"To investigate the cost-effectiveness of pharmacogenetic-guided phenprocoumon dosing versus standard anticoagulation care in Dutch patients with atrial fibrillation."( Cost-effectiveness of pharmacogenetic-guided dosing of phenprocoumon in atrial fibrillation.
Beltman, PA; de Boer, A; Maitland-van der Zee, AH; Redekop, WK; Thariani, R; van Schie, RM; Veenstra, DL; Verhoef, TI, 2013
)
0.88
"Compared with standard care, the pharmacogenetic-guided dosing strategy increased quality-adjusted life-years (QALYs) only very slightly and increased costs by €15."( Cost-effectiveness of pharmacogenetic-guided dosing of phenprocoumon in atrial fibrillation.
Beltman, PA; de Boer, A; Maitland-van der Zee, AH; Redekop, WK; Thariani, R; van Schie, RM; Veenstra, DL; Verhoef, TI, 2013
)
0.64
"Pharmacogenetic-guided dosing of phenprocoumon has the potential to increase health slightly and may be able to achieve this in a cost-effective way."( Cost-effectiveness of pharmacogenetic-guided dosing of phenprocoumon in atrial fibrillation.
Beltman, PA; de Boer, A; Maitland-van der Zee, AH; Redekop, WK; Thariani, R; van Schie, RM; Veenstra, DL; Verhoef, TI, 2013
)
0.92
" Because there is a large inter-individual and intra-individual variability in dose-response and a small therapeutic window, treatment with coumarin derivatives is challenging."( Pharmacogenetic-guided dosing of coumarin anticoagulants: algorithms for warfarin, acenocoumarol and phenprocoumon.
Daly, AK; de Boer, A; Maitland-van der Zee, AH; Redekop, WK; van Schie, RM; Verhoef, TI, 2014
)
0.62
"Observational evidence suggests that the use of a genotype-guided dosing algorithm may increase the effectiveness and safety of acenocoumarol and phenprocoumon therapy."( A randomized trial of genotype-guided dosing of acenocoumarol and phenprocoumon.
Barallon, R; de Boer, A; Kolovou, G; Kolovou, V; Konstantinides, S; Le Cessie, S; Maitland-van der Zee, AH; Maltezos, E; Manolopoulos, VG; Ragia, G; Redekop, WK; Remkes, M; Rosendaal, FR; Tavridou, A; Tziakas, D; van der Meer, FJ; van Schie, RM; Verhoef, TI; Wadelius, M, 2013
)
0.83
"We conducted two single-blind, randomized trials comparing a genotype-guided dosing algorithm that included clinical variables and genotyping for CYP2C9 and VKORC1 with a dosing algorithm that included only clinical variables, for the initiation of acenocoumarol or phenprocoumon treatment in patients with atrial fibrillation or venous thromboembolism."( A randomized trial of genotype-guided dosing of acenocoumarol and phenprocoumon.
Barallon, R; de Boer, A; Kolovou, G; Kolovou, V; Konstantinides, S; Le Cessie, S; Maitland-van der Zee, AH; Maltezos, E; Manolopoulos, VG; Ragia, G; Redekop, WK; Remkes, M; Rosendaal, FR; Tavridou, A; Tziakas, D; van der Meer, FJ; van Schie, RM; Verhoef, TI; Wadelius, M, 2013
)
0.81
"6% for patients receiving genotype-guided dosing and 60."( A randomized trial of genotype-guided dosing of acenocoumarol and phenprocoumon.
Barallon, R; de Boer, A; Kolovou, G; Kolovou, V; Konstantinides, S; Le Cessie, S; Maitland-van der Zee, AH; Maltezos, E; Manolopoulos, VG; Ragia, G; Redekop, WK; Remkes, M; Rosendaal, FR; Tavridou, A; Tziakas, D; van der Meer, FJ; van Schie, RM; Verhoef, TI; Wadelius, M, 2013
)
0.63
"Genotype-guided dosing of acenocoumarol or phenprocoumon did not improve the percentage of time in the therapeutic INR range during the 12 weeks after the initiation of therapy."( A randomized trial of genotype-guided dosing of acenocoumarol and phenprocoumon.
Barallon, R; de Boer, A; Kolovou, G; Kolovou, V; Konstantinides, S; Le Cessie, S; Maitland-van der Zee, AH; Maltezos, E; Manolopoulos, VG; Ragia, G; Redekop, WK; Remkes, M; Rosendaal, FR; Tavridou, A; Tziakas, D; van der Meer, FJ; van Schie, RM; Verhoef, TI; Wadelius, M, 2013
)
0.89
"To investigate the influence of metformin use on the dosage of phenprocoumon and INR in stably anticoagulated patients."( Metformin use decreases the anticoagulant effect of phenprocoumon.
Lijfering, WM; van de Riet, IR; van der Meer, FJ; Wijnen, JC, 2014
)
0.89
"This study shows that clinicians should be aware that metformin treatment may lead to an increased optimal dosage of phenprocoumon."( Metformin use decreases the anticoagulant effect of phenprocoumon.
Lijfering, WM; van de Riet, IR; van der Meer, FJ; Wijnen, JC, 2014
)
0.86
" The PPC-INR-response curve resulting from physician guided dosage was compared to INR values calculated by "twin calculation" from TheMa recommended dosage."( [Computer aided dosage management of phenprocoumon anticoagulation therapy. Clinical validation].
Cromme, LJ; Dissmann, R; Gäbler, F; Heyne, K; Kunath, J; Salzwedel, A; Taborski, U; Völler, H, 2014
)
0.68
" The clinical usefulness of genotype-guided dosing of warfarin has been previously assessed in randomized clinical trials that were limited by lack of power and inconsistent results."( Genotype-guided vs clinical dosing of warfarin and its analogues: meta-analysis of randomized clinical trials.
Brown, DL; Stergiopoulos, K, 2014
)
0.4
"To compare genotype-guided initial dosing of warfarin and its analogues with clinical dosing protocols."( Genotype-guided vs clinical dosing of warfarin and its analogues: meta-analysis of randomized clinical trials.
Brown, DL; Stergiopoulos, K, 2014
)
0.4
"MEDLINE (inception to December 31, 2013), EMBASE (inception to December 31, 2013), and the Cochrane Library Central Register of Controlled Trials (inception to December 31, 2013) were searched for randomized clinical trials comparing genotype-guided warfarin dosing vs clinical dosing for adults with indications for anticoagulation."( Genotype-guided vs clinical dosing of warfarin and its analogues: meta-analysis of randomized clinical trials.
Brown, DL; Stergiopoulos, K, 2014
)
0.4
"In 9 trials, 2812 patients were randomized to receive warfarin, acenocoumarol, or phenprocoumon according to a genotype-guided algorithm or a clinical dosing algorithm."( Genotype-guided vs clinical dosing of warfarin and its analogues: meta-analysis of randomized clinical trials.
Brown, DL; Stergiopoulos, K, 2014
)
0.63
"In this meta-analysis of randomized clinical trials, a genotype-guided dosing strategy did not result in a greater percentage of time that the INR was within the therapeutic range, fewer patients with an INR greater than 4, or a reduction in major bleeding or thromboembolic events compared with clinical dosing algorithms."( Genotype-guided vs clinical dosing of warfarin and its analogues: meta-analysis of randomized clinical trials.
Brown, DL; Stergiopoulos, K, 2014
)
0.4
" Coagulation biomarkers in shed blood were assessed at 3 h after monotherapy with the medicines under study, at 3 h after triple therapy dosing and at steady state trough conditions."( Antithrombotic triple therapy and coagulation activation at the site of thrombus formation: a randomized trial in healthy subjects.
Eichinger, S; Gouya, G; Kapiotis, S; Kyrle, PA; Litschauer, B; Mayer, P; Smerda, L; Weisshaar, S; Wolzt, M, 2014
)
0.4
" However, the safe use of coumarin anticoagulants is restricted by a narrow therapeutic window and large interindividual dosing variations."( Genotype-Guided Dosing of Coumarin Anticoagulants: A Meta-analysis of Randomized Controlled Trials.
Chen, L; Cheng, J; Han, S; Jia, Z; Li, M; Liu, J; Lu, C; Pei, E; Tang, T; Xu, J; Ye, M; Zhang, X; Zuo, K, 2015
)
0.42
"Four electronic databases were searched from January 1, 2000, to March 1, 2014, for randomized controlled trials of patients who received coumarin anticoagulants according to genotype-guided dosing algorithms."( Genotype-Guided Dosing of Coumarin Anticoagulants: A Meta-analysis of Randomized Controlled Trials.
Chen, L; Cheng, J; Han, S; Jia, Z; Li, M; Liu, J; Lu, C; Pei, E; Tang, T; Xu, J; Ye, M; Zhang, X; Zuo, K, 2015
)
0.42
"This meta-analysis showed that genotype-guided dosing increased the effectiveness and safety of coumarin therapy compared with standard dosing but did not have advantages compared with clinical variables-guided dosing."( Genotype-Guided Dosing of Coumarin Anticoagulants: A Meta-analysis of Randomized Controlled Trials.
Chen, L; Cheng, J; Han, S; Jia, Z; Li, M; Liu, J; Lu, C; Pei, E; Tang, T; Xu, J; Ye, M; Zhang, X; Zuo, K, 2015
)
0.42
"To investigate the cost-effectiveness of a pharmacogenetic dosing algorithm versus a clinical dosing algorithm for coumarin anticoagulants in The Netherlands."( Economic evaluation of a pharmacogenetic dosing algorithm for coumarin anticoagulants in The Netherlands.
de Boer, A; Maitland-van der Zee, AH; Redekop, WK; Verhoef, TI, 2015
)
0.42
"A decision-analytic Markov model was used to analyze the cost-effectiveness of pharmacogenetic dosing of phenprocoumon and acenocoumarol versus clinical dosing."( Economic evaluation of a pharmacogenetic dosing algorithm for coumarin anticoagulants in The Netherlands.
de Boer, A; Maitland-van der Zee, AH; Redekop, WK; Verhoef, TI, 2015
)
0.63
"Pharmacogenetic dosing improves health only slightly when compared with clinical dosing."( Economic evaluation of a pharmacogenetic dosing algorithm for coumarin anticoagulants in The Netherlands.
de Boer, A; Maitland-van der Zee, AH; Redekop, WK; Verhoef, TI, 2015
)
0.42
"It has not been investigated how much the use of clinical factors in a dosing algorithm improves the percentage of time in therapeutic range (TTR)."( Comparison of dosing algorithms for acenocoumarol and phenprocoumon using clinical factors with the standard care in the Netherlands.
de Boer, A; Le Cessie, S; Maitland-van der Zee, AH; van der Meer, FJ; Verhoef, TI; Zhang, Y, 2015
)
0.67
" Data from the Dutch patients in the EU-PACT trial (comparing the use of a clinical algorithm with and without genetic information) was used for the clinical dosing algorithm."( Comparison of dosing algorithms for acenocoumarol and phenprocoumon using clinical factors with the standard care in the Netherlands.
de Boer, A; Le Cessie, S; Maitland-van der Zee, AH; van der Meer, FJ; Verhoef, TI; Zhang, Y, 2015
)
0.67
"During the weeks 2-12, the clinical dosing algorithm of acenocoumarol (80 patients) led to a higher TTR (74."( Comparison of dosing algorithms for acenocoumarol and phenprocoumon using clinical factors with the standard care in the Netherlands.
de Boer, A; Le Cessie, S; Maitland-van der Zee, AH; van der Meer, FJ; Verhoef, TI; Zhang, Y, 2015
)
0.67
"The use of a clinical dosing algorithm for acenocoumarol seemed to improve the quality of anticoagulation therapy during the treatment of initial 2-12 weeks."( Comparison of dosing algorithms for acenocoumarol and phenprocoumon using clinical factors with the standard care in the Netherlands.
de Boer, A; Le Cessie, S; Maitland-van der Zee, AH; van der Meer, FJ; Verhoef, TI; Zhang, Y, 2015
)
0.67
" Based on current evidence, clinicians should include body weight, along with other established variables when dosing VKA."( Effect of Body Weight on Dose of Vitamin K Antagonists.
Sakaan, S; Sands, CW; Self, TH; Wallace, JL, 2015
)
0.42
"The direct oral anticoagulants (DOAC) dabigatran, rivaroxaban, and apixaban are increasingly prescribed in atrial fibrillation (AF) patients, although dosage in elderly patients, safety in chronic kidney disease, food- and drug-interactions, laboratory tests for monitoring, and antidote are not clarified."( A Probable Life-Saving Switch from Apixaban to Phenprocoumon.
Finsterer, J; Stöllberger, C, 2015
)
0.67
" Validation was by comparing actual dosing to algorithm predictions."( Optimization of vitamin K antagonist drug dose finding by replacement of the international normalized ratio by a bidirectional factor: validation of a new algorithm.
Beinema, MJ; Brouwers, JR; Rosendaal, FR; van der Meer, FJ, 2016
)
0.43
" Validation was by comparing actual dosing to algorithm predictions."( Optimization of vitamin K antagonist drug dose finding by replacement of the international normalized ratio by a bidirectional factor: validation of a new algorithm.
Beinema, MJ; Brouwers, JR; Rosendaal, FR; van der Meer, FJ, 2016
)
0.43
" Improvement of VKA dosing defined as more time in therapeutic range (TTR) can reduce thrombotic disease and bleeding."( Optimization of vitamin K antagonist drug dose finding by replacement of the international normalized ratio by a bidirectional factor: validation of a new algorithm.
Beinema, MJ; Brouwers, JR; Rosendaal, FR; van der Meer, FJ, 2016
)
0.43
" The rate of automated dosage proposals increased to 100%."( Optimization of vitamin K antagonist drug dose finding by replacement of the international normalized ratio by a bidirectional factor: validation of a new algorithm.
Beinema, MJ; Brouwers, JR; Rosendaal, FR; van der Meer, FJ, 2016
)
0.43
"The BF-N algorithm performs well in real-life settings and increases the rate of automated dosage proposals."( Optimization of vitamin K antagonist drug dose finding by replacement of the international normalized ratio by a bidirectional factor: validation of a new algorithm.
Beinema, MJ; Brouwers, JR; Rosendaal, FR; van der Meer, FJ, 2016
)
0.43
"VKORC polymorphism affects PC dosage in the initiation as well as the maintenance phase."( Genetic variations of phenprocoumon metabolism in patients with ventricular assist devices.
Beyersdorf, F; Brehm, K; Heilmann, C; Krumnau, O, 2016
)
0.75
" The VKA dosage (mg/day) after statin initiation was compared with the last VKA dosage before the statin was started."( Statin use decreases coagulation in users of vitamin K antagonists.
Biedermann, JS; Bonafacio, SM; Kruip, MJ; Lijfering, WM; van der Meer, FJ; van Rein, N, 2016
)
0.43
"Initiation of statin treatment was associated with an immediate and long-term minor although statistically significant decrease in VKA dosage in both phenprocoumon and acenocoumarol users, which suggests that statins may have anticoagulant properties."( Statin use decreases coagulation in users of vitamin K antagonists.
Biedermann, JS; Bonafacio, SM; Kruip, MJ; Lijfering, WM; van der Meer, FJ; van Rein, N, 2016
)
0.63
" The results support the use of genotype-guided dosing for phenprocoumon in patients < 75 years."( Age-stratified outcome of a genotype-guided dosing algorithm for acenocoumarol and phenprocoumon.
de Boer, A; Le Cessie, S; Maitland-van der Zee, AH; Manolopoulos, VG; van der Meer, FJ; Verhoef, TI; Zhang, Y, 2017
)
0.92
" Objectives To investigate the effect of genotype-guided dosing stratified by age and the potential factors causing a difference."( Age-stratified outcome of a genotype-guided dosing algorithm for acenocoumarol and phenprocoumon.
de Boer, A; Le Cessie, S; Maitland-van der Zee, AH; Manolopoulos, VG; van der Meer, FJ; Verhoef, TI; Zhang, Y, 2017
)
0.68
"Essentials Prospective studies of pharmacogenetic-guided (PG) coumarin dosing produced varying results."( Dosing algorithms for vitamin K antagonists across VKORC1 and CYP2C9 genotypes.
Asselbergs, FW; Baranova, EV; de Boer, A; le Cessie, S; Maitland-van der Zee, AH; Manolopoulos, VG; Ragia, G; Verhoef, TI, 2017
)
0.46
"Background The multicenter, single-blind, randomized EU-PACT trial compared the safety and efficacy of genotype-guided and non-genetic dosing algorithms for acenocoumarol and phenprocoumon in patients with atrial fibrillation or deep vein thrombosis."( Dosing algorithms for vitamin K antagonists across VKORC1 and CYP2C9 genotypes.
Asselbergs, FW; Baranova, EV; de Boer, A; le Cessie, S; Maitland-van der Zee, AH; Manolopoulos, VG; Ragia, G; Verhoef, TI, 2017
)
0.65
" The vascular complication rate after PSS was independent of intraprocedural heparin dosage and activated clotting time."( How safe are NOACs compared with phenprocoumon after pulmonary vein isolation with the cryoballoon technique using purse-string suture closure?
Akkaya, E; Berkowitsch, A; Deubner, N; Greiss, H; Hain, A; Hamm, CW; Kuniss, M; Neumann, T; Sperzel, J; Zaltsberg, S, 2017
)
0.74
" Genetic polymorphisms account for high VKA dosage variability."( Meta-Analysis of Genotype-Guided Versus Standard Dosing of Vitamin K Antagonists.
Abdalla, A; Ahmed, S; Bachuwa, G; Hassan, M; Haykal, T; Kheiri, B; Osman, M, 2018
)
0.48
"To study the effects of clinical and genetic factors on the phenprocoumon dose requirement in pediatric patients and to develop a dosing algorithm."( Effects of age and genetic variations in VKORC1, CYP2C9 and CYP3A4 on the phenprocoumon dose in pediatric patients.
Appel, IM; Bierings, MB; Boer, A; Cessie, SL; der Straaten, TV; Maagdenberg, H; Maitland-van der Zee, AH; Swen, JJ; Tamminga, RY; van der Meer, FJ; van Ommen, CH, 2018
)
0.95
" We observed no dose-response relationship (e."( Use of vitamin K antagonists and risk of prostate cancer: Meta-analysis and nationwide case-control study.
Friis, S; Jensen, PH; Kristensen, KB; Pottegård, A; Skriver, C, 2019
)
0.51
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (2)

RoleDescription
anticoagulantAn agent that prevents blood clotting.
EC 1.6.5.2 [NAD(P)H dehydrogenase (quinone)] inhibitorAn EC 1.6.5.* (oxidoreductase acting on NADH or NADPH with a quinone or similar as acceptor) inhibitor that interferes with the action of NAD(P)H dehydrogenase (quinone), EC 1.6.5.2.
[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 (1)

ClassDescription
hydroxycoumarinAny coumarin carrying at least one hydroxy substituent.
[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]

Pathways (2)

PathwayProteinsCompounds
Phenprocoumon Action Pathway203
Effect of intestinal microbiome on anticoagulant response of vitamin K antagonists413

Protein Targets (5)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Spike glycoproteinSevere acute respiratory syndrome-related coronavirusPotency3.16230.009610.525035.4813AID1479145
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Gag-Pol polyproteinHuman immunodeficiency virus type 2 (ISOLATE ROD)Ki1.00000.00000.07851.0000AID1794850
Cytochrome P450 2D6Homo sapiens (human)IC50 (µMol)528.00000.00002.015110.0000AID262947
Gag-Pol polyproteinHuman immunodeficiency virus type 1 (NEW YORK-5 ISOLATE)Ki1.00000.00000.12203.1000AID1794850
Protease Human immunodeficiency virus 1IC50 (µMol)1.00000.00010.22487.3200AID241288
Protease Human immunodeficiency virus 1Ki0.70020.00000.04433.1000AID160271; AID160287; AID160437; AID160610
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (16)

Processvia Protein(s)Taxonomy
xenobiotic metabolic processCytochrome P450 2D6Homo sapiens (human)
steroid metabolic processCytochrome P450 2D6Homo sapiens (human)
cholesterol metabolic processCytochrome P450 2D6Homo sapiens (human)
estrogen metabolic processCytochrome P450 2D6Homo sapiens (human)
coumarin metabolic processCytochrome P450 2D6Homo sapiens (human)
alkaloid metabolic processCytochrome P450 2D6Homo sapiens (human)
alkaloid catabolic processCytochrome P450 2D6Homo sapiens (human)
monoterpenoid metabolic processCytochrome P450 2D6Homo sapiens (human)
isoquinoline alkaloid metabolic processCytochrome P450 2D6Homo sapiens (human)
xenobiotic catabolic processCytochrome P450 2D6Homo sapiens (human)
retinol metabolic processCytochrome P450 2D6Homo sapiens (human)
long-chain fatty acid biosynthetic processCytochrome P450 2D6Homo sapiens (human)
negative regulation of bindingCytochrome P450 2D6Homo sapiens (human)
oxidative demethylationCytochrome P450 2D6Homo sapiens (human)
negative regulation of cellular organofluorine metabolic processCytochrome P450 2D6Homo sapiens (human)
arachidonic acid metabolic processCytochrome P450 2D6Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (8)

Processvia Protein(s)Taxonomy
monooxygenase activityCytochrome P450 2D6Homo sapiens (human)
iron ion bindingCytochrome P450 2D6Homo sapiens (human)
oxidoreductase activityCytochrome P450 2D6Homo sapiens (human)
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygenCytochrome P450 2D6Homo sapiens (human)
heme bindingCytochrome P450 2D6Homo sapiens (human)
anandamide 8,9 epoxidase activityCytochrome P450 2D6Homo sapiens (human)
anandamide 11,12 epoxidase activityCytochrome P450 2D6Homo sapiens (human)
anandamide 14,15 epoxidase activityCytochrome P450 2D6Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (6)

Processvia Protein(s)Taxonomy
mitochondrionCytochrome P450 2D6Homo sapiens (human)
endoplasmic reticulumCytochrome P450 2D6Homo sapiens (human)
endoplasmic reticulum membraneCytochrome P450 2D6Homo sapiens (human)
cytoplasmCytochrome P450 2D6Homo sapiens (human)
intracellular membrane-bounded organelleCytochrome P450 2D6Homo sapiens (human)
virion membraneSpike glycoproteinSevere acute respiratory syndrome-related coronavirus
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (42)

Assay IDTitleYearJournalArticle
AID1079947Comments (NB not yet translated). [column 'COMMENTAIRES' in source]
AID1079939Cirrhosis, proven histopathologically. Value is number of references indexed. [column 'CIRRH' in source]
AID78477Ability to bind to guinea pig atrial homogenate1980Journal of medicinal chemistry, May, Volume: 23, Issue:5
Accumulation of drugs by guinea pig isolated atria. Quantitative correlations.
AID1079933Acute liver toxicity defined via clinical observations and clear clinical-chemistry results: serum ALT or AST activity > 6 N or serum alkaline phosphatases activity > 1.7 N. This category includes cytolytic, choleostatic and mixed liver toxicity. Value is
AID588211Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in humans2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID155794Tested for antiviral activity in HIV-1 infected PBMC; 100-3001994Journal of medicinal chemistry, Sep-30, Volume: 37, Issue:20
Structure-based design of HIV protease inhibitors: 4-hydroxycoumarins and 4-hydroxy-2-pyrones as non-peptidic inhibitors.
AID1439677Inhibition of VKORC1 in rat liver microsomes in presence of 0.003 to 0.2 mM vitamin K2017Bioorganic & medicinal chemistry letters, 04-01, Volume: 27, Issue:7
Synthesis and biological evaluation of C-3 aliphatic coumarins as vitamin K antagonists.
AID1079945Animal toxicity known. [column 'TOXIC' in source]
AID262947Inhibition of human CYP2D6 expressed in Escherichia coli JM1092006Journal of medicinal chemistry, Apr-20, Volume: 49, Issue:8
Catalytic site prediction and virtual screening of cytochrome P450 2D6 substrates by consideration of water and rescoring in automated docking.
AID1079949Proposed mechanism(s) of liver damage. [column 'MEC' in source]
AID160287Binding affinity towards HIV protease was determined1996Journal of medicinal chemistry, Sep-27, Volume: 39, Issue:20
Cycloalkylpyranones and cycloalkyldihydropyrones as HIV protease inhibitors: exploring the impact of ring size on structure-activity relationships.
AID1079944Benign tumor, proven histopathologically. Value is number of references indexed. [column 'T.BEN' in source]
AID1079934Highest frequency of acute liver toxicity observed during clinical trials, expressed as a percentage. [column '% AIGUE' in source]
AID91480Ability to bind to human serum albumin (HSA)1980Journal of medicinal chemistry, May, Volume: 23, Issue:5
Accumulation of drugs by guinea pig isolated atria. Quantitative correlations.
AID160610Tested for the HIV Protease inhibitory activity of the compound1994Journal of medicinal chemistry, Sep-30, Volume: 37, Issue:20
Structure-based design of HIV protease inhibitors: 4-hydroxycoumarins and 4-hydroxy-2-pyrones as non-peptidic inhibitors.
AID1439678Anticoagulant activity in Sprague-Dawley rat assessed as increase of prothombin time at 10 mg/kg, po after 24 hrs relative to control2017Bioorganic & medicinal chemistry letters, 04-01, Volume: 27, Issue:7
Synthesis and biological evaluation of C-3 aliphatic coumarins as vitamin K antagonists.
AID1079946Presence of at least one case with successful reintroduction. [column 'REINT' in source]
AID293981Inhibition of rat microsomal VKER2007Bioorganic & medicinal chemistry, Mar-15, Volume: 15, Issue:6
Synthesis and structure-activity relationships of novel warfarin derivatives.
AID1079935Cytolytic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is > 5 (see ACUTE). Value is number of references indexed. [column 'CYTOL' in source]
AID588213Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in non-rodents2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID1439683Drug uptake in Sprague-Dawley rat liver assessed per gram of liver at 10 mg/kg, po after 72 hrs by HPLC-UV analysis2017Bioorganic & medicinal chemistry letters, 04-01, Volume: 27, Issue:7
Synthesis and biological evaluation of C-3 aliphatic coumarins as vitamin K antagonists.
AID1439681Drug uptake in Sprague-Dawley rat liver assessed per gram of liver at 10 mg/kg, po after 24 hrs by HPLC-UV analysis2017Bioorganic & medicinal chemistry letters, 04-01, Volume: 27, Issue:7
Synthesis and biological evaluation of C-3 aliphatic coumarins as vitamin K antagonists.
AID1079941Liver damage due to vascular disease: peliosis hepatitis, hepatic veno-occlusive disease, Budd-Chiari syndrome. Value is number of references indexed. [column 'VASC' in source]
AID1079932Highest frequency of moderate liver toxicity observed during clinical trials, expressed as a percentage. [column '% BIOL' in source]
AID1079948Times to onset, minimal and maximal, observed in the indexed observations. [column 'DELAI' in source]
AID1079936Choleostatic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is < 2 (see ACUTE). Value is number of references indexed. [column 'CHOLE' in source]
AID588212Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in rodents2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID1079931Moderate liver toxicity, defined via clinical-chemistry results: ALT or AST serum activity 6 times the normal upper limit (N) or alkaline phosphatase serum activity of 1.7 N. Value is number of references indexed. [column 'BIOL' in source]
AID1079938Chronic liver disease either proven histopathologically, or through a chonic elevation of serum amino-transferase activity after 6 months. Value is number of references indexed. [column 'CHRON' in source]
AID241288Inhibitory concentration against human immunodeficiency virus 1 protease in MT-4 cells2005Bioorganic & medicinal chemistry letters, Jul-01, Volume: 15, Issue:13
Design, synthesis, and biological evaluation of novel 4-hydroxypyrone derivatives as HIV-1 protease inhibitors.
AID1439680Anticoagulant activity in Sprague-Dawley rat assessed as increase of prothombin time at 10 mg/kg, po after 72 hrs relative to control2017Bioorganic & medicinal chemistry letters, 04-01, Volume: 27, Issue:7
Synthesis and biological evaluation of C-3 aliphatic coumarins as vitamin K antagonists.
AID25870Tested for the dissociation constant of the compound1980Journal of medicinal chemistry, May, Volume: 23, Issue:5
Accumulation of drugs by guinea pig isolated atria. Quantitative correlations.
AID1079940Granulomatous liver disease, proven histopathologically. Value is number of references indexed. [column 'GRAN' in source]
AID160437Tested for inhibition of HIV protease1996Journal of medicinal chemistry, Oct-25, Volume: 39, Issue:22
Structure-based design of HIV protease inhibitors: sulfonamide-containing 5,6-dihydro-4-hydroxy-2-pyrones as non-peptidic inhibitors.
AID1079943Malignant tumor, proven histopathologically. Value is number of references indexed. [column 'T.MAL' in source]
AID1079942Steatosis, proven histopathologically. Value is number of references indexed. [column 'STEAT' in source]
AID160271Binding affinity against HIV-1 protease1997Journal of medicinal chemistry, Mar-28, Volume: 40, Issue:7
Structure-based design of nonpeptidic HIV protease inhibitors: the sulfonamide-substituted cyclooctylpyramones.
AID23672Partition coefficient (logP)1980Journal of medicinal chemistry, May, Volume: 23, Issue:5
Accumulation of drugs by guinea pig isolated atria. Quantitative correlations.
AID1079937Severe hepatitis, defined as possibly life-threatening liver failure or through clinical observations. Value is number of references indexed. [column 'MASS' in source]
AID1794850Protease Inhibition Assay from Article 10.1021/jm00046a002: \\Structure-based design of HIV protease inhibitors: 4-hydroxycoumarins and 4-hydroxy-2-pyrones as non-peptidic inhibitors.\\1994Journal of medicinal chemistry, Sep-30, Volume: 37, Issue:20
Structure-based design of HIV protease inhibitors: 4-hydroxycoumarins and 4-hydroxy-2-pyrones as non-peptidic inhibitors.
AID588220Literature-mined public compounds from Kruhlak et al phospholipidosis modelling dataset2008Toxicology mechanisms and methods, , Volume: 18, Issue:2-3
Development of a phospholipidosis database and predictive quantitative structure-activity relationship (QSAR) models.
AID1346138Human vitamin K epoxide reductase complex subunit 1 (1.-.-.- Oxidoreductases)1952Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.), Dec, Volume: 81, Issue:3
Effect in man of a new indandione anticoagulant.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (960)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990297 (30.94)18.7374
1990's176 (18.33)18.2507
2000's244 (25.42)29.6817
2010's222 (23.13)24.3611
2020's21 (2.19)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 56.89

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 very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index56.89 (24.57)
Research Supply Index7.02 (2.92)
Research Growth Index4.47 (4.65)
Search Engine Demand Index96.40 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (56.89)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials124 (12.54%)5.53%
Reviews45 (4.55%)6.00%
Case Studies249 (25.18%)4.05%
Observational18 (1.82%)0.25%
Other553 (55.92%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (23)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Prospective, Randomized, Open-Label, Blinded Endpoint Evaluation (PROBE) Parallel Group Study Comparing Edoxaban vs. VKA in Subjects Undergoing Catheter Ablation of Non-valvular Atrial Fibrillation (ELIMINATE-AF) [NCT02942576]Phase 3632 participants (Actual)Interventional2017-03-21Completed
Impact of Dabigatran and Phenprocoumon on ADP Induced Platelet Aggregation in Patients With Atrial Fibrillation [NCT01339819]Phase 470 participants (Actual)Interventional2011-04-30Completed
Influence of Rivaroxaban Compared to Vitamin K Antagonist Treatment Upon Development of Cardiovascular Calcification in Patients With Atrial Fibrillation and/ or Pulmonary Embolism (IRIVASC- Trial) [NCT02066662]Phase 4192 participants (Actual)Interventional2013-07-31Completed
Long-term Treatment for Cancer Patients With Deep Venous Thrombosis or Pulmonary Embolism [NCT01164046]Phase 356 participants (Actual)Interventional2010-08-31Terminated(stopped due to Due to slow inclusion of patients)
Left Atrial Appendage CLOSURE in Patients With Atrial Fibrillation at High Risk of Stroke and Bleeding Compared to Medical Therapy: a Prospective Randomized Clinical Trial [NCT03463317]Phase 41,512 participants (Anticipated)Interventional2018-02-28Recruiting
An Investigator-driven, Prospective, Parallel-group, Randomised, Open, Blinded Outcome Assessment (PROBE), Multi-centre Trial to Determine the Optimal Anticoagulation Therapy for Patients Untergoing Catheter Ablation of Atrial Fibrillation [NCT02227550]Phase 4676 participants (Actual)Interventional2014-12-31Completed
Real-world Comparative Effectiveness of Stroke Prevention in Patients With Atrial Fibrillation Treated With Factor Xa Non-vitamin-K Oral Anticoagulants (NOACs) vs. Phenprocoumon [NCT03563937]64,920 participants (Actual)Observational2018-06-15Completed
Impact of Dabigatran and Phenprocoumon on Clopidogrel Mediated ADP Induced Platelet Aggregation in Patients With Atrial Fibrillation [NCT01352702]Phase 446 participants (Actual)Interventional2011-05-31Terminated(stopped due to Slow recruitment; Study was terminated for futility reasons)
Pilot-Trial: Dabigatran as an Alternative Anticoagulant in Patients With Left Ventricular Assist Device [NCT02872649]Phase 216 participants (Actual)Interventional2013-01-31Terminated(stopped due to safety reasons)
Effects of Dabigatran in Patients With AF - A Prospective, Randomized, Open-label, Explorative, Blinded-endpoint Trial to Compare the Efficacy of Dabigatran With Phenprocoumon for the Resolution of LAA Thrombus in Patients With AF [NCT02256683]Phase 264 participants (Actual)Interventional2014-07-31Terminated(stopped due to Recruiting problems)
Rivaroxaban Versus Vitamin K-Antagonist (VKA) in Thromboprophylaxis of Patients With Atrial Fibrillation: Patient Preference Study [NCT02090543]647 participants (Actual)Observational2014-01-31Completed
Safety and Efficacy of a D-Dimer-Guided Strategy for Extension of Secondary Prophylaxis of Venous Thromboembolism - a Prospective and Randomized Management Trial [NCT00895505]Phase 3300 participants (Anticipated)Interventional2008-02-29Recruiting
Real-world Comparative Effectiveness of Rivaroxaban Versus Low-molecular-weight Heparin (LMWH) and Phenprocoumon for the Treatment and Secondary Prevention of Venous Thromboembolism (RECENT) [NCT04444804]22,153 participants (Actual)Observational2020-07-31Completed
Prospective Randomized Trial of a Clinical Algorithm to Predict the Loading Dose of Phenprocoumon [NCT00586287]Phase 4302 participants (Actual)Interventional2007-01-31Completed
Biomarkers and Antithrombotic Treatment in Cervical Artery Dissection - TREAT-CAD [NCT02046460]Phase 4194 participants (Actual)Interventional2013-09-30Completed
Phenprocoumon Versus Dabigatran in Subjects With Atrial Fibrillation and Left Atrial Thrombus - a Prospective, Randomized, Controlled, Open-label One Year Follow-up Pilot Study [NCT02591225]Phase 440 participants (Anticipated)Interventional2015-10-31Recruiting
A PHASE I, OPEN-LABEL, MULTICENTER, RANDOMINZED, PARALELL STUDY TO INVESTIGATE THE EFFECT OF VEMURAFENIB ON THE PHARMACOKINETICS OF A SINGLE ORAL DOSE OF PHENPROCOUMON IN PATIENTS WITH BRAFV600 MUTATION-POSITIVE METASTATIC MALIGNANCY [NCT01849666]Phase 12 participants (Actual)Interventional2013-09-30Completed
Effects of Very Low Dose Oral Anticoagulation on Thromboembolism and Bleeding Events in Patients With Mechanical Heart Valve Replacement [NCT00528671]Phase 41,571 participants (Actual)Interventional2006-01-31Terminated
Real-world Comparative Effectiveness of Stroke Prevention in Patients With Atrial Fibrillation Treated With Rivaroxaban vs. Vitamin k Antagonists [NCT02960880]99,999 participants (Actual)Observational2016-10-15Completed
Prospective Study on the Treatment of Unsuspected Pulmonary Embolism in Cancer Patients [NCT01727427]695 participants (Actual)Observational2012-11-30Completed
A Prospective, Randomized, Controlled, Analyst-blinded, Parallel Group Study to Investigate the Effect of Antithrombotic Triple Therapy With Ticagrelor and Acetylsalicylic Acid in Combination With Dabigatran or Rivaroxaban or Phenprocoumon on Markers of C [NCT01812200]Phase 460 participants (Actual)Interventional2012-10-31Completed
Drug Persistence/Adherence in Patients Being Treated With Dabigatran Etexilate or VKA for Stroke Prevention in Non-valvular Atrial Fibrillation (SPAF) [NCT02240667]1,506 participants (Actual)Observational2014-09-18Completed
A Safety Study Assessing Oral Anticoagulation With Apixaban Versus Vitamin-K Antagonists in Patients With Atrial Fibrillation (AF) and End-Stage Kidney Disease (ESKD) on Chronic Hemodialysis Treatment [NCT02933697]Phase 3108 participants (Actual)Interventional2017-06-20Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT02240667 (3) [back to overview]Percentage of Patients Treated With Anticoagulation Initially Started at the 12 Month
NCT02240667 (3) [back to overview]Percentage of Patients With Low, Medium or High Adherence at the Timepoint of 6 Months-visit.
NCT02240667 (3) [back to overview]Number of Patients With the Reason for Definitive Treatment Discontinuation
NCT02942576 (4) [back to overview]Number of Participants Who Experienced Major Bleeding (International Society on Thrombosis and Hemostasis [ISTH]) in the Edoxaban Group Compared With VKA Group Among Participants Undergoing Catheter Ablation (Adjudicated Data)
NCT02942576 (4) [back to overview]Number of Participants Who Experienced the Composite of All-cause Death, Stroke (Alternative), and Major Bleeding (ISTH) in the Edoxaban Group Compared With VKA Group Among Participants Undergoing Catheter Ablation (Adjudicated Data)
NCT02942576 (4) [back to overview]Number of Participants Who Experienced the Composite of All-cause Death, Stroke (VARC-2), and Major Bleeding (ISTH) in the Edoxaban Group Compared With Vitamin K Antagonist (VKA) Group in Participants Undergoing Catheter Ablation (Adjudicated Data)
NCT02942576 (4) [back to overview]Number of Participants Who Experienced the Composite of Stroke (VARC-2), Systemic Embolic Events (SEE), and Cardiovascular (CV) Mortality in the Edoxaban Group Compared With VKA Group Among Participants Undergoing Catheter Ablation (Adjudicated Data)

Percentage of Patients Treated With Anticoagulation Initially Started at the 12 Month

Percentage of patients treated with the initially allocated anticoagulant at the 12-month visit, defined as Kaplan Meier estimate at 12 months for persistence, stratified for dabigatran etexilate and VKA.Persistence is defined as the time between initiation and permanent discontinuation of therapy. The initiation date is the documented start of treatment (at visit 1), and the date of permanent discontinuation is the documented permanent discontinuation of dabigatran etexilate or VKA therapy. (NCT02240667)
Timeframe: 12 month (Visit 5)

Interventionpercentage of participants (Number)
Dabigatran (Dabigatran vs VKA)89.5
VKA (Dabigatran vs VKA)89.5

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Percentage of Patients With Low, Medium or High Adherence at the Timepoint of 6 Months-visit.

Percentage of patients with low, medium or high adherence at the 6-month visit, stratified for dabigatran etexilate and VKA; categorisation is done on the basis of the Morisky questionnaire (high, medium and low adherence with a Morisky score of 0, 1 to 2, and > 2, respectively). (NCT02240667)
Timeframe: 6 month (visit 3)

,
InterventionPercentage of participants (Number)
LowMediumHighMissing
Dabigatran (Dabigatran vs VKA)19.1245.85.8829.2
VKA (Dabigatran vs VKA)23.7446.853.9925.42

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Number of Patients With the Reason for Definitive Treatment Discontinuation

Number of patients with the reason for definitive treatment discontinuation (NCT02240667)
Timeframe: Visit 2, 3, 4 and 5 (after approx. 3, 6, 9 and 12 months of treatment)

InterventionParticipants (Count of Participants)
Visit 2 (Month 3)72081633Visit 2 (Month 3)72081634Visit 3 (Month 6)72081633Visit 3 (Month 6)72081634Visit 4 (Month 9)72081633Visit 4 (Month 9)72081634Visit 5 (Month 12)72081633Visit 5 (Month 12)72081634
Patient's wishDecision of physicianOtherSerious adverse event
Dabigatran (Dabigatran vs VKA)1
VKA (Dabigatran vs VKA)1
Dabigatran (Dabigatran vs VKA)0
VKA (Dabigatran vs VKA)2
Dabigatran (Dabigatran vs VKA)2
VKA (Dabigatran vs VKA)0

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Number of Participants Who Experienced Major Bleeding (International Society on Thrombosis and Hemostasis [ISTH]) in the Edoxaban Group Compared With VKA Group Among Participants Undergoing Catheter Ablation (Adjudicated Data)

Major bleeding was defined by the International Society on Thrombosis and Hemostasis (ISTH) as fatal bleeding and/or bleeding that is symptomatic and occurs in a critical area or organ and/or extrasurgical site bleeding causing a fall in hemoglobin level of >2 g/dL or leads to blood transfusion, surgical site bleeding that requires a second intervention, causes hemarthrosis that delays mobilization or wound healing, or causes hemodynamic instability. (NCT02942576)
Timeframe: Day 1 to Day 90

InterventionParticipants (Count of Participants)
Edoxaban-based Regimen10
VKA-based Regimen3

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Number of Participants Who Experienced the Composite of All-cause Death, Stroke (Alternative), and Major Bleeding (ISTH) in the Edoxaban Group Compared With VKA Group Among Participants Undergoing Catheter Ablation (Adjudicated Data)

"An alternative definition characterized stroke (ischemic, hemorrhagic, or undetermined) as an abrupt onset, over minutes to hours, of a focal neurological deficit in the distribution of a single brain artery that was not due to an identifiable nonvascular cause (ie, brain tumor or trauma), and that either lasted at least 24 hours or resulted in death within 24 hours of onset.~Major bleeding was defined by the International Society on Thrombosis and Hemostasis (ISTH) as fatal bleeding and/or bleeding that is symptomatic and occurs in a critical area or organ and/or extrasurgical site bleeding causing a fall in hemoglobin level of >2 g/dL or leads to blood transfusion, surgical site bleeding that requires a second intervention, causes hemarthrosis that delays mobilization or wound healing, or causes hemodynamic instability." (NCT02942576)
Timeframe: Day 1 to Day 90

InterventionParticipants (Count of Participants)
Edoxaban-based Regimen1
VKA-based Regimen2

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Number of Participants Who Experienced the Composite of All-cause Death, Stroke (VARC-2), and Major Bleeding (ISTH) in the Edoxaban Group Compared With Vitamin K Antagonist (VKA) Group in Participants Undergoing Catheter Ablation (Adjudicated Data)

"Stroke (ischemic, hemorrhagic, or undetermined) was defined by Valve Academic Research Consortium-2 (VARC-2) as an acute episode of focal or global neurological dysfunction caused by brain, spinal cord, or retinal vascular injury following hemorrhage or infarction. A stroke event was based on any of the following: duration of neurological dysfunction >24 hours (h), duration of neurological dysfunction <24 h in case of imaging-documented new hemorrhage or infarction, and a neurological dysfunction resulting in death.~Major bleeding was defined by the International Society on Thrombosis and Hemostasis (ISTH) as fatal bleeding and/or bleeding that is symptomatic and occurs in a critical area or organ and/or extrasurgical site bleeding causing a fall in hemoglobin level of >2 g/dL or leads to blood transfusion, surgical site bleeding that requires a second intervention, causes hemarthrosis that delays mobilization or wound healing, or causes hemodynamic instability." (NCT02942576)
Timeframe: Day 1 to Day 90

InterventionParticipants (Count of Participants)
Edoxaban-based Regimen1
VKA-based Regimen2

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Number of Participants Who Experienced the Composite of Stroke (VARC-2), Systemic Embolic Events (SEE), and Cardiovascular (CV) Mortality in the Edoxaban Group Compared With VKA Group Among Participants Undergoing Catheter Ablation (Adjudicated Data)

"Stroke (ischemic, hemorrhagic, or undetermined) was defined by Valve Academic Research Consortium-2 (VARC-2) as an acute episode of focal or global neurological dysfunction caused by brain, spinal cord, or retinal vascular injury following hemorrhage or infarction. A stroke event was based on any of the following: duration of neurological dysfunction >24 hours (h), duration of neurological dysfunction <24 h in case of imaging-documented new hemorrhage or infarction, and a neurological dysfunction resulting in death.~SEE was defined as an arterial embolism resulting in clinical ischemia, excluding the central nervous system, coronary, and pulmonary arterial circulation.~CV mortality was defined as cardiac or vascular death according to Academic Research Consortium." (NCT02942576)
Timeframe: Day 1 to Day 90

InterventionParticipants (Count of Participants)
Edoxaban-based Regimen1
VKA-based Regimen0

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