Effect of roxithromycin on the pharmacokinetics of lovastatin in volunteers

Objective: To investigate the influence of concomitant administration of roxithromycin on the plasma pharmacokinctics of lovastatin. Methods: In an open, randomized, crossover study, 12 healthy volunteers received 80 mg lovastatin orally either alone or concomitantly with 300 mg roxithromycin after 5-day pretreatment with roxithromycin 30 mg daily. Plasma concentrations of lovastatin (lactone and acid) were determined using high-performance liquid chromatography, and the pharmacokinetic parameters were estimated. Results: The mean (+/-SD) pharmacokinetic parameters of lovastatin lactone with and without roxithromycin were maximum concentration (C-max) 8.49 +/- 6.80/16.3 +/- 9.4ng ml(-1), time to Cmax (t(max)) 1.8 +/- 04/1.7 +/- 0.6h, terminal plasma half-life (t(1/2)) 4.3 +/- 2.0/3.7 +/- 2.5 h, area under the plasma concentration-time curve from zero to infinity (AUC(0) (infinity)) 53 +/- 60/85 +/- 67 ng ml(-1) h. The respective parameters of lovastatin acid were C-max 24.6 +/- 13.4/17.8 +/- 11.0 ng ml(-1), t(max) 3.7 +/- 1.1/4.1 +/- 0.7 h, t(1/2) 3.2 +/- 2.5/4.3 +/- 2.8 h, AUC(0) (infinity) 149 +/- 123/105 +/- 58 ng ml(-1) h. Mean bioavailability of lovastatin lactone was lower and that of lovastatin acid was higher with concomitant treatment. However, the differences were significant only with respect to lovastatin lactone (AUC and C-max) and C-max of lovastatin acid. Conclusion: Roxithromycin does not influence the pharmacokinetics of lovastatin in such a way that dosage adjustment of lovastatin seems to be necessary during co-administration.