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 (Cmax) 8.49+/-6.80/16.3+/-9.4 ng ml(-1), time to Cmax (tmax) 1.8+/-0.4/1.7+/-0.6 h, terminal plasma half-life (t1/2) 4.3+/-2.0/3.7+/-2.5 h, area under the plasma concentration-time curve from zero to infinity (AUC0-infinity) 53+/-60/85+/-67 ng ml(-1) h. The respective parameters of lovastatin acid were Cmax 24.6+/-13.4/17.8+/-11.0 ng ml(-1), tmax 3.7+/-1.1/4.1+/-0.7 h, t1/2 3.2+/-2.5/4.3+/-2.8 h, AUC0-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 Cmax) and Cmax of lovastatin acid.


CONCLUSIONS
Roxithromycin does not influence the pharmacokinetics of lovastatin in such a way that dosage adjustment of lovastatin seems to be necessary during co-administration.
Bucher
M
M
Department of Anesthesiology, University of Regensburg, Germany.
Mair
G
G
Kees
F
F
D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000924:Anticholesteremic Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D005260:Female; D006207:Half-Life; D006801:Humans; D008148:Lovastatin / Q000493:pharmacokinetics*; D008297:Male; D015575:Roxithromycin / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D000924:Anticholesteremic Agents; D015575:Roxithromycin; D008148:Lovastatin