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 C(max) 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 AUC(0-48 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 C(max) and AUC(0-48 h) values of lovastatin acid. Results from this study demonstrated as the dose of ER-lovastatin increased from 10 to 40 mg, the C(max) and AUC(0-48 h) values of lovastatin as well as lovastatin acid appeared to increase linearly.
Lamson
Michael
M
Andrx Laboratories Inc., Ft. Lauderdale, FL 33314, USA. mlamson@andrx.com
Phillips
Gale
G
Shen
Jason
J
Lukacsko
Peter
P
Friedhoff
Lawrence
L
Niecestro
Robert M
RM
D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008148:Lovastatin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male
D003692:Delayed-Action Preparations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin