Establishment and verification of cytochrome P450 3 A enzyme induction model in female rats
- Author:
Zong-Ling XIA
1
Author Information
- Publication Type:Journal Article
- Keywords: CYP3A4; Female SD rat; Metabolism kinetics model
- From: Chinese Pharmaceutical Journal 2013;48(12):995-999
- CountryChina
- Language:Chinese
- Abstract: OBJECTIVE: To establish a female rat CYP3A induction model which is used for studying CYP3A-mediated drug-drug interactions. METHODS: Female SD rats which were fed with standard diet were randomly divided into two groups, one was the control group, and the other one was the experimental group. The rats in the experimental group were administered respectively 20, 50, 80, 100, and 150 mg·g-1d-1 dexamethasone by gavage for 3 d to induce CYP3A enzymes. 24 h after 3 d, liver tissues were taken from both groups of rats and rat liver microsomes were prepared. CYP3A4 activity was determined with testosterone as the probe substrate. RESULTS: Testosterone metabolic rate was 31.68% in blank liver microsomes, and were 40.64%, 61.36%, 82.44%, 85.8%, and 83.36% in dexamethasone-induction group. Testosterone metabolic rate was improved by up to 160.23% after dexamethasone induction at 80 mg·g-1d-1 in female rats. CONCLUSION: Dexamethasone induction at 80 mg·g-1d-1 can significantly increase liver CYP3A enzyme activity in female SD rats, and the model can be used to study CYP3A-mediated drug-drug interactions.
