1.School of Pharmaceutical Science, Shanxi Medical University, Taiyuan 030001, China;
2. Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education), Department of Pharmacy, Peking University Cancer Hospital & Institute, Beijing 100142,China
Abstract��
Objective To study the in vitro metabolism and enzyme kinetics of di-n-butyl-(4-chlorobenzohydroxamato) tin(IV) chloride in rat liver microsomes, and to identify the major cytochrome P450 isozymes involved in the metabolism of di-n-butyl-(4-chlorobenzohydroxamato) tin(IV) chloride in rat liver microsomes. Methods By optimizing the incubation conditions of di-n-butyl-(4-chlorobenzohydroxamato) tin(IV) chloride in rat liver microsomes, the enzyme kinetics in different enzyme sources was researched; the cytochrome P450 isozymes involved in metabolism of di-n-butyl-(4-chlorobenzohydroxamato) tin(IV) chloride were preliminarily explored through in vitro inhibition experiments. Results Different enzyme source metabolism experiments showed that between phenobarbital(PB) and desamethasone(Dex) induction groups and blank control group there had significant differences, but between the BNF group and blank control group there had no significant difference; the inhibition experiments revealed that ketoconazole had strong inhibition effect on di-n-butyl-(4-chlorobenzohydroxamato) tin(IV) chloride metabolism. Conclusion CYP3A plays a leading role in di-n-butyl-(4-chlorobenzohydroxamato) tin(IV) chloride metabolism, and CYP2C9 may be partly involved. CYP1A has no catalysis action on metabolism of di-n-butyl-(4-chlorobenzohydroxamato) tin(IV) chloride. The Results suggest that attention should be paid to the possibility of drug interactions when di-n-butyl-(4-chlorobenzohydroxamato) tin(IV) chloride is combined with the drugs metabolized by above-mentioned isozymes.
PING Yao-Dong-,
,
ZHANG Li-Feng- etc
.Research of in vitro Metabolism of Di-n-butyl-(4-chlorobenzohydroxamato) Tin(IV) Chloride in Rat liver Microsomes[J] Chinese Pharmaceutical Journal, 2013,V48(13): 1065-1068
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2013, Vol. 48 
