Effects of roxithromycin, a new semisynthetic macrolide, and two erythromycins on drug metabolizing enzymes in rat liver.
The effects of a new semisynthetic macrolide, roxithromycin, on drug metabolizing enzymes of rat liver were compared with two erythromycins, the base (EB) and the estolate (EE), after 7 days' treatment with high oral doses (400 and 800 mg/kg daily). Dose-related higher concentrations of roxithromycin were reached in serum and liver than after EB or EE. The two reference erythromycins induced the synthesis of microsomal enzymes and formed inactive cytochrome P-450-metabolite complexes. N-Demethylation of erythromycin itself and aminopyrine was increased by the treatment. Liver microsomal enzyme activities were not induced and the inactive cytochrome P-450-metabolite complex was not formed after 400 mg/kg of roxithromycin and only to a very limited extent after 800 mg/kg (10% vs. 50% after EE). At the higher dose microsomal activities were not changed by roxithromycin and only aminopyrine N-demethylation was reduced.
Villa
P
P
Laboratory of Toxicology and Isolated Organ Perfusion, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Sassella
D
D
Corada
M
M
Bartosek
I
I
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003640:Dealkylation; D004305:Dose-Response Relationship, Drug; D004917:Erythromycin / Q000378:metabolism / Q000494:pharmacology*; D007933:Leucomycins / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000900:Anti-Bacterial Agents; D007933:Leucomycins; D004364:Pharmaceutical Preparations; D004917:Erythromycin