Back to Search
Start Over
Sex-dependent pharmacokinetics and in vitro reductive metabolism of acetohexamide in Wistar-Imamichi rats.
- Source :
-
Biological & pharmaceutical bulletin [Biol Pharm Bull] 1999 Apr; Vol. 22 (4), pp. 435-8. - Publication Year :
- 1999
-
Abstract
- A significant sex-related difference was observed for the pharmacokinetics of acetohexamide in Wistar-Imamichi (Wistar-IM) rats. However, there was no sex difference of the in vitro reductive metabolism of acetohexamide in the liver or kidney of these rats. Testectomy was found to decrease the plasma clearance (CLp) of acetohexamide in male rats, whereas ovariectomy had no effect on the CLp of acetohexamide in female animals, suggesting that androgens regulate the pharmacokinetics of acetohexamide. The co-administration of sulfamethazine, which is known to be metabolized by a male-specific cytochrome P450 (CYP) isoform (CYP2C11), significantly decreased the CLp of acetohexamide in male Wistar-IM rats. Based on these results, it is reasonable to assume that the sex-dependent pharmacokinetics of acetohexamide observed in Wistar-IM rats is associated with the male-specific hydroxylation catalyzed by CYP2C11.
- Subjects :
- Acetohexamide administration & dosage
Acetohexamide metabolism
Animals
Female
Hypoglycemic Agents administration & dosage
Hypoglycemic Agents metabolism
Male
Orchiectomy
Ovariectomy
Oxidation-Reduction
Rats
Rats, Wistar
Sex Factors
Sulfamethazine administration & dosage
Sulfamethazine pharmacology
Acetohexamide pharmacokinetics
Hypoglycemic Agents pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 0918-6158
- Volume :
- 22
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Biological & pharmaceutical bulletin
- Publication Type :
- Academic Journal
- Accession number :
- 10328570
- Full Text :
- https://doi.org/10.1248/bpb.22.435