ABSTRACT
AIM: 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. CONCLUSION: The O-demethyl-RXM was an active metabolite in humans, and there were some species differences in RXM demethylation metabolism between humans and rats.
Subject(s)
Anti-Bacterial Agents/metabolism , Roxithromycin/analogs & derivatives , Roxithromycin/metabolism , Adolescent , Adult , Aged , Animals , Anti-Bacterial Agents/pharmacokinetics , Bacillus subtilis/drug effects , Female , Humans , Male , Methylation , Micrococcus luteus/drug effects , Middle Aged , Rats , Rats, Wistar , Roxithromycin/pharmacokinetics , Roxithromycin/pharmacology , Species SpecificityABSTRACT
Effects of macrolide antibiotic, roxithromycin (RXM) on human lymphocytes in culture were studied. The drug showed a dose-dependent inhibition of 3H-thymidine and 35S-methionine uptake responding to T cell mitogens and purified protein derivative of tuberculin (PPD). Activation by PPD, as assessed by 3H-thymidine uptake, was more sensitive to inhibition than the response to T cell mitogens. The drug produced a loss of blasts when added soon after transformation commenced. Immunosuppressive effects of RXM were further characterized by using four different types of metabolized RXM, RU 28111, RU 39001, RU 44981 and RU 45179. The most potent inhibitor of lymphocyte transformation was RU 45179, followed by RU 44981, RU 39001 and RU 28111 have little activity.