Pharmacokinetics of lovastatin extended-release dosage form (Lovastatin XL) in healthy volunteers

The purpose of this study was to evaluate pharmacokinetics and dose proportionality of lovastatin extended‐release dosage form (ER‐lovastatin) in the dosage levels of 10, 20 and 40 mg in 9 healthy male subjects. Each subject was randomized to receive a single oral dose of ER‐lovastatin either 10, 20 or 40 mg in a three‐way crossover design with a washout period of 7 days between the treatments. Subjects were served dinner at approximately 5:30 PM followed by dosing at approximately 10:00 PM in each study period. Serial plasma samples were collected up to 48 h after dosing and assayed for lovastatin and its active metabolite lovastatin acid using an LC/MS/MS method. The plasma concentration–time profiles of lovastatin and its active metabolite lovastatin acid exhibited delayed‐ and extended‐release characteristics at each dose. Mean (±) values for the Cmax of lovastatin were 1.04±0.43, 2.03±0.65 and 4.03±3.02 ng/ml for the 10, 20 and 40 mg dosage, respectively. The corresponding values for the AUC0–48 h of lovastatin were 14.6±7.8, 34.1 ±13.7, and 53.9±35.6 ng h/ml. The same tendency was also found for Cmax and AUC0−48 h values of lovastatin acid. Results from this study demonstrated as the dose of ER‐lovastatin increased from 10 to 40 mg, the Cmax and AUC0−48 h values of lovastatin as well as lovastatin acid appeared to increase linearly. Copyright © 2002 John Wiley & Sons, Ltd.