Effects of cefetamet hydrochloride injection on activity of CYP1A2, CYP3A4 and CYP2E1 in liver microsomes of rats / 第二军医大学学报

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 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.