TY - JOUR AU - ZHONG Da-Fang AU - ZHANG Shu-Qiu AU - SUN Lu AU - ZHAO Xiao-Yu PY - 2016 TI - Metabolism of roxithromycin in phenobarbital-treated rat liver microsomes. JF - Acta Pharmacologica Sinica; Vol 23, No 5 (May 2002): Acta Pharmacologica Sinica Y2 - 2016 KW - N2 - AIM: To investigate the metabolism of roxithromycin (RXM) in rat liver microsomes and the possible effects of RXM and its metabolites on cytochrome P-450 (CYP450). METHODS: Liver microsomes of Wistar rats, induced by phenobarbital, were prepared using ultracentrifuge method. RXM in vitro metabolism was stu died with the microsome incubation. The metabolites were separated and assayed by li quid chromatography-tandem mass spectrometry (LC-MSn), and were further identified by comparison of their mass spectra and LC behavior to synthesized references. RESULTS: N-Mono- and N-di-demethyl metabolites a s well as O-dealkylated metabolite (erythromycin oxime) were detected in microsomal incubates. RXM and its metabolites expressed weak potency to form inactive complexes with CYP450. CONCLUSION: N-Demethylation and oxime ether side chain O- dealkylation are main biotransformation pathways of RXM in phenobarbital-treated rat liver microsomes. Both routes were found to be NADPH-dependent. RXM and its metabolites showed weak inhibitory effects on CYP450. UR - http://www.chinaphar.com/article/view/7589