No effect of short-term omeprazole intake on acenocoumarol pharmacokinetics and pharmacodynamics

被引:13
作者
deHoon, JNJM
Thijssen, HHW
Beysens, AJMM
VanBortel, LMAB
机构
[1] MAASTRICHT UNIV,DEPT PHARMACOL,CARDIOVASC RES INST MAASTRICHT,NL-6200 MD MAASTRICHT,NETHERLANDS
[2] UNIV LIMBURG,ACAD HOSP MAASTRICHT,MAASTRICHT,NETHERLANDS
关键词
drug interaction; acenocoumarol; omeprazole; oral anticoagulants;
D O I
10.1046/j.1365-2125.1997.00600.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Aims To investigate the effect of omeprazole on the pharmacokinetics of R- and S-acenocoumarol and on their combined anticoagulant activity. Methods Eight healthy male subjects completed a double-blind, randomized, placebo-controlled, two-way cross-over study. Subjects were given either omeprazole 40 mg or placebo once daily for 3 days. On day 2 of each study period, a single 10 mg oral dose of racemic acenocoumarol was administered and venous blood samples were collected for pharmacokinetic and pharmacodynamic assessments. A wash-out period of 2 weeks separated the two study periods. Results The pharmacokinetics of R-and S-acenocoumarol (AUG 3016 +/- 221 and 233 +/- 14 ng ml(-1) h, respectively) did not change after omeprazole (AUG 2929 +/- 256 and 220 +/- 18 ng ml(-1) h, respectively). Anticoagulant activity (INRmax 1.7 +/- 0.1) was unaffected by co-administration of omeprazole (INRmax 1.7 +/- 0.1). Conclusions The shea-term intake of omeprazole does not affect acenocoumarol pharmacokinetics or pharmacodynamics. These data differ from the results of previous studies on the effect of omeprazole on warfarin, suggesting a different in vivo interaction profile of omeprazole on acenocoumarol than on warfarin. Drug interaction studies with oral anticoagulants should not be restricted to the use of warfarin.
引用
收藏
页码:399 / 401
页数:3
相关论文
共 16 条
  • [1] PHARMACOKINETICS AND BIOAVAILABILITY OF OMEPRAZOLE AFTER SINGLE AND REPEATED ORAL-ADMINISTRATION IN HEALTHY-SUBJECTS
    ANDERSSON, T
    ANDREN, K
    CEDERBERG, C
    LAGERSTROM, PO
    LUNDBORG, P
    SKANBERG, I
    [J]. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1990, 29 (05) : 557 - 563
  • [2] IDENTIFICATION OF HUMAN LIVER CYTOCHROME-P450 ISOFORMS MEDIATING OMEPRAZOLE METABOLISM
    ANDERSSON, T
    MINERS, JO
    VERONESE, ME
    TASSANEEYAKUL, W
    TASSANEEYAKUL, W
    MEYER, UA
    BIRKETT, DJ
    [J]. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1993, 36 (06) : 521 - 530
  • [3] SLOW OMEPRAZOLE METABOLIZERS ARE ALSO POOR S-MEPHENYTOIN HYDROXYLATORS
    ANDERSSON, T
    REGARDH, CG
    DAHLPUUSTINEN, ML
    BERTILSSON, L
    [J]. THERAPEUTIC DRUG MONITORING, 1990, 12 (04) : 415 - 416
  • [4] BRECKENRIDGE A, 1974, CLIN PHARMACOL THER, V15, P424
  • [5] MODEL TO DETECT WARFARIN-DRUG INTERACTIONS IN MAN
    DUURSEMA, L
    MULLER, FO
    HUNDT, HKL
    HEYNS, AD
    MEYER, BH
    LUUS, HG
    [J]. DRUG INVESTIGATION, 1992, 4 (05): : 395 - 402
  • [6] POSSIBLE POTENTIATION OF ANTICOAGULANT EFFECT OF ACENOCOUMAROL BY OMEPRAZOLE
    GARCIA, B
    LACAMBRA, C
    GARROTE, F
    GARCIAPLAZA, I
    SOLIS, J
    [J]. PHARMACY WORLD & SCIENCE, 1994, 16 (05): : 231 - 232
  • [7] STEREOSPECIFIC ASSAY OF NICOUMALONE - APPLICATION TO PHARMACOKINETIC STUDIES IN MAN
    GILL, TS
    HOPKINS, KJ
    ROWLAND, M
    [J]. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1988, 25 (05) : 591 - 598
  • [8] OMEPRAZOLE INHIBITS OXIDATIVE DRUG-METABOLISM - STUDIES WITH DIAZEPAM AND PHENYTOIN INVIVO AND 7-ETHOXYCOUMARIN INVITRO
    GUGLER, R
    JENSEN, JC
    [J]. GASTROENTEROLOGY, 1985, 89 (06) : 1235 - 1241
  • [9] HUMAN LIVER MICROSOMAL METABOLISM OF THE ENANTIOMERS OF WARFARIN AND ACENOCOUMAROL - P450 ISOZYME DIVERSITY DETERMINES THE DIFFERENCES IN THEIR PHARMACOKINETICS
    HERMANS, JJR
    THIJSSEN, HHW
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 1993, 110 (01) : 482 - 490
  • [10] HIRSH J, 1991, NEW ENGL J MED, V324, P1865