Demethylation metabolism of roxithromycin in humans and rats.
OBJECTIVE
To investigate the demethylated metabolites of roxithromycin (RXM) in humans and rats, and to study the antibiotic activity of these metabolites in vitro.


METHODS
The demethylated metabolites of RXM in humans and in rats were identified by liquid chromatography-mass spectrometry (LC-MS), and the in vitro antibiotic activities of them against three standard strains were also studied compared with those of the parent drug and some other metabolites of RXM.


RESULTS
O-Demethylation of RXM was one of the main metabolic routes of RXM in humans, whereas N-demethylation metabolism was more predominant in rats. O-Demethyl-RXM appeared to be equally effective with RXM.


CONCLUSIONS
The O-demethyl-RXM was an active metabolite in humans, and there were some species differences in RXM demethylation metabolism between humans and rats.
Li
X Q
XQ
Laboratory of Drug Metabolism and Pharmacokinetics, Shenyang Pharmaceutical University, Shenyang 110016, China.
Zhong
D F
DF
Huang
H H
HH
Wu
S D
SD
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000493:pharmacokinetics; D001412:Bacillus subtilis / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008745:Methylation; D016982:Micrococcus luteus / Q000187:drug effects; D008875:Middle Aged; D051381:Rats; D017208:Rats, Wistar; D015575:Roxithromycin / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D013045:Species Specificity
D000900:Anti-Bacterial Agents; C478422:O-demethyl-roxithromycin; D015575:Roxithromycin