Subject Area物理化学
Metabolism of cephalomannine in human liver microsomes
Zhang JW(张江伟); Ge GB(葛广波); Liu Y(刘勇); Zhang YY(张延延); Liu XB(刘兴宝); Cheng J(程婕); Li W(李巍); Yang L(杨凌)
Conference Name第三届中日双边药理学和临床药理学会议
Conference Date2007-8-23
Conference Place中国
Funding Organization中国药理学会
AbstractTo identify the metabolites of cephalomannine and cytochrome P450 (CYP) isoforms involved. METHODS LC/MS/MS was recruited to identify the possible structures of metabolites. Incubations were conducted with CYP isoform specific inhibitors and recombinant human CYP isoforms to ascribe individual reaction to a single CYP isoform. RESULTS After incubated with human liver microsomes (HLMs) and NADPH-generating system, two mono-hydroxylated metabolites of cephalomannine were eluted at 6.5 and 10.9 min respectively. C4'''' (6.5 min) and C6α (10.9 min) were identified as the possible hydroxylation sites by LC/MS/MS. Chemical inhibition studies and assays with recombinant CYPs suggested that 4''''-hydroxycephalomannine was produced exclusively by CYP3A4 and 6α-hydroxycephalomannine by CYP2C8. Different from the metabolism of paclitaxel, 4''''-hydroxycephalomannine by CYP3A4 became the dominant metabolite, and the mean ratio of 4''''-hydroxycephalomannine to 6α-hydroxycephalomannine was 64:36 in three liver microsomes. CONCLUSION Cephalomannine differs from paclitaxel with regard to major hydroxylation site and main metabolism enzyme. Our results confirm that substituents in C3'' greatly impact taxane metabolism. Key words: cephalomannine (taxol B); cytochrome P450 (CYP); taxane; paclitaxel
Document Type会议论文
Corresponding AuthorYang L(杨凌)
Recommended Citation
GB/T 7714
Zhang JW,Ge GB,Liu Y,et al. Metabolism of cephalomannine in human liver microsomes[C],2007:357/2.
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