Effect of roxithromycin on the pharmacokinetics of lovastatin in volunteers.

Objective: To investigate the influence of concomitant administration of roxithromycin on the plasma pharmacokinetics 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 300 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±9.4 ng ml^–1, time to C_max (t_max) 1.8±0.4/1.7±0.6 h, 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–∞) 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–∞ 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. [ABSTRACT FROM AUTHOR]