Original Article

Metabolism of roxithromycin in phenobarbital-treated rat liver microsomes.

Authors: Da-Fang ZHONG, Shu-Qiu ZHANG, Lu SUN, Xiao-Yu ZHAO

Abstract

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.
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