Metabolism of roxithromycin in phenobarbital-treated rat liver microsomes.
OBJECTIVE
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.


CONCLUSIONS
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.
Zhong
Da-Fang
DF
Laboratory of Drug Metabolism and Pharmecokinetics, Shengyang Pharmaceutical University, Shenyang 110016, China. zhongdf@ihw.com.cn
Zhang
Shu-Qiu
SQ
Sun
Lu
L
Zhao
Xiao-Yun
XY
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015575:Roxithromycin / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D015575:Roxithromycin; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital