Effects of cefetamet hydrochloride injection on activity of CYP1A2, CYP3A4 and CYP2E1 in liver microsomes of rats
10.3724/SP.J.1008.2013.01231
- Author:
Song LI
1
Author Information
1. Department of Pharmaceutical Analysis, School of Pharmacy, Second Military Medical University, Key Laboratory of Shanghai Drug (Chinese Materia Medica) Metabolism Research
- Publication Type:Journal Article
- Keywords:
Cefetamet;
Cytochrome P-450 CYP1A2;
Cytochrome P-450 CYP2E1;
Cytochrome P-450 CYP3A4;
Liver microsomes
- From:
Academic Journal of Second Military Medical University
2013;34(11):1231-1236
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the effect of cefetamet hydrochloride injection on the activity of 3 kinds of cytochrome P450 (CYP450) isoforms (CYP1A2, CYP3A4 and CYP2E1) in rat liver microsomes. Methods The SD rats were randomly divided into two groups: control group and cefetamet hydrochloride (CH) group, with each group containing 3 male rats and 3 female rats. The CH group was injected with cefetamet hydrochloride into the tail vein at 50 mg/(kg • d), twice a day for 7 days. A HPLC method was used for simultaneous determination of the production of metabolites and the degradation of the prototype probe substrates of 3 kinds of CYP450 isoforms, so as to evaluate the activity of hepatic CYP450. The analytical column was Diamonsil C18 column (150 mm X 4. 6 mm, 5 Fm), with the flow rate being 1. 0 mL/min. The mobile phase consisted of methanol (0. 1% formic acid) (A)-water (0. 1% formic acid)(B), 0-5 min; 18%A, 5-10 min; 18%-60%A, 10-15 min: 60%A and detected at 247 nm for determination of CYP1A2 activities; methanol (A)-water (0. 02% formic acid)(B), 0-11 min: 40%-60%A and detected at 223 nm for determination of CYP3A4 activities; and methanol (A)-water, 0-10 min: 37%-75%A and detected at 287 nm for determination of CYP2E1 activities. Results Probe substrates and their metabolites showed good linearity within the determining range (r≥0. 999 7). The precision of the method was < 6% (n = 5) and extraction recoveries were 83. 2%-97. 5%. After 7-day injection of CH,CYP3A4 activities were significantly different between the two groups (P<0. 05); CYP1A2 and CYP2E1 activities were not significantly different between the two groups (P>0. 05). Conclusion CH injection can significantly induce hepatic microsome CYP3A4 expression in SD rats, but has no induction or inhibition effect on CYP1A2 and CYP2E1, indicating that potential drug-drug interaction might occur when CH injection is coadministered with drugs metabolized by CYP3A4.
