抄録
The effects of clarithromycin and erythromycin estolate on hepatic drug-metabolizing enzyme capacity in Sprague Dawley (SD) and Wistar strain rats were studied. Effects of both antibiotics on hepatic microsomal drugmetabolizing enzymes were estimated by antipyrine pharmacokinetics and the formation rates of 3-hydroxymethyl antipyrine (HMA), 4-hydroxyantipyrine (OHA) and norantipyrine (NORA), and by the serum ratio of dimethadione to trimethadione (DMO/TMO) . In SD rats, both clarithromycin and erythromycin estolate significantly decreased formation clearance of OHA (CLHHA ) after single and multiple dosing. Clearances of NORA (CLNOHA) and HMA (CLHMA) tended to decrease after 5 days of treatment with clarithromycin.
Erythromycin estolate significantly decreased CLNORA after 5 days of treatment but tended to increase CLHMA. In Wistar rats, both CLHMA and CLNORA were significantly decreased with clarithromycin for 5 days but CLOHA did not show any significant changes with the drug treatment. For trimethadione metabolism, 5 days of treatment with clarithromycin increased the serum concentration ratio of DMO/TMO from 0.51±0.1 to 0.72±0.06 in SD rats, but significantly decreased the ratio from 0.84±0.06 to 0.53±0.06 (p<0.01) in Wistar rats. Clarithromycin increased the hepatic microsomal concentration of CYP 1A1, 2C 11 and decreased CYP3A2 in both SD and Wistar rats by Western blot analysis. With clarithromycin, the content of CYP2C13 was decreased in Wistar rats but increased in SD rats. In conclusion, the inhibition and the induction mechanism of clarithromycin and erythromycin estolate on hepatic drug metabolyzing enzyme system may be different between SD and Wistar rats.
