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Gender difference in the pharmacokinetic interaction between oral warfarin and oxolamine in rats: inhibition of CYP2B1 by oxolamine in male rats
Biopharmaceutics & drug disposition, 2007-04, Vol.28 (3), p.125-133
Zhu, Xuan
Lee, Dae Y.
Shin, Wan G.
2007
Volltextzugriff (PDF)
Details
Autor(en) / Beteiligte
Zhu, Xuan
Lee, Dae Y.
Shin, Wan G.
Titel
Gender difference in the pharmacokinetic interaction between oral warfarin and oxolamine in rats: inhibition of CYP2B1 by oxolamine in male rats
Ist Teil von
Biopharmaceutics & drug disposition, 2007-04, Vol.28 (3), p.125-133
Ort / Verlag
Chichester, UK: John Wiley & Sons, Ltd
Erscheinungsjahr
2007
Quelle
MEDLINE
Beschreibungen/Notizen
The possible reason for the significantly greater AUC of oral warfarin with oral oxolamine in male Sprague−Dawley rats was evaluated. After oral administration of warfarin at a dose of 2 mg/kg to male rats with oxolamine at doses of 10 and 50 mg/kg, the AUC values of warfarin were significantly greater than the controls (254 and 330 versus 180 µg h/ml). However, the AUC values of warfarin were not affected by oxolamine in female rats. This could be due to inhibition of CYP2B1, 2C11 and 3A2 by oxolamine in male rats, since warfarin was metabolized via CYP1A1, 2B1, 2C6, 2C11 and 3A2 in rats and CYP2B1 is male dominant, and CYP2C11 and 3A2 are male specific. Therefore, phenytoin, torasemide and clarithromycin (mainly metabolized via CYP2B1/2, 2C11 and 3A2 in rats, respectively) were administered intravenously to male rats with or without oral oxolamine. After oral oxolamine at doses of 10 and 50 mg/kg, the AUC of phenytoin was significantly greater (1280 and 1640 versus 938 µg min/ml), however, the AUC values of torasemide and clarithromycin were independent of oxolamine. The above data suggest that the significantly greater AUC of oral warfarin with oral oxolamine could be due to inhibition of CYP2B1/2 by oxolamine in male rats. Copyright © 2007 John Wiley & Sons, Ltd.
Sprache
Englisch
Identifikatoren
ISSN: 0142-2782
eISSN: 1099-081X
DOI: 10.1002/bdd.538
Titel-ID: cdi_crossref_primary_10_1002_bdd_538
Format
–
Schlagworte
Administration, Oral
,
Animals
,
Anti-Inflammatory Agents, Non-Steroidal - administration & dosage
,
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
,
Anticoagulants - pharmacokinetics
,
Area Under Curve
,
Clarithromycin - pharmacokinetics
,
CYP2B1
,
Cytochrome P-450 CYP2B1 - drug effects
,
Cytochrome P-450 CYP2B1 - metabolism
,
Cytochrome P-450 Enzyme System - drug effects
,
Cytochrome P-450 Enzyme System - metabolism
,
Dose-Response Relationship, Drug
,
Drug Interactions
,
Female
,
Male
,
Oxadiazoles - administration & dosage
,
Oxadiazoles - pharmacology
,
oxolamine
,
pharmacokinetic interaction
,
Phenytoin - pharmacokinetics
,
Protein Binding
,
Rats
,
Rats, Sprague-Dawley
,
Sex Factors
,
Sulfonamides - pharmacokinetics
,
warfarin
,
Warfarin - pharmacokinetics
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