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Pharmacokinetics of lovastatin extended‐release dosage form (Lovastatin XL) in healthy volunteers
Author(s) -
Lamson Michael,
Phillips Gale,
Shen Jason,
Lukacsko Peter,
Friedhoff Lawrence,
Niecestro Robert M.
Publication year - 2002
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.304
Subject(s) - lovastatin , pharmacokinetics , pharmacology , metabolite , dosing , chemistry , crossover study , medicine , chromatography , cholesterol , biochemistry , alternative medicine , pathology , placebo
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. Copyright © 2002 John Wiley & Sons, Ltd.