Comparative pharmacokinetics of lovastatin extended-release tablets and lovastatin immediate-release tablets in humans.
The pharmacokinetics of lovastatin and its active metabolite lovastatin acid was evaluated in 9 healthy subjects in a three-period crossover study following a single oral dose of lovastatin extended-release (ER) tablets and lovastatin immediate-release (IR) tablets. Participants were dosed with lovastatin IR 40 mg tablets following a standard breakfast, lovastatin ER 40 mg tablets following a standard breakfast, and lovastatin ER 40 mg tablets underfasting conditions. Serial plasma samples were collected for up to 48 hours postdose and assayed for lovastatin and lovastatin acid using a liquid chromatography/mass spectroscopy/mass spectroscopy method. Lovastatin ER tablets, unlike lovastatin IR tablets, exhibited delayed- and extended-release characteristics. The relative bioavailability, in terms of area under the curve values, of lovastatin (156%) and lovastatin acid (124%) was greater from lovastatin ER tablets as compared with lovastatin IR tablets when given with breakfast. An even greater increase in the bioavailability of lovastatin (261%) and lovastatin acid (231%) was observed when the lovastatin ER tablets were administered under fasting conditions. Thus, greater gastrointestinal tract drug absorption of lovastatin from lovastatin ER tablets was demonstrated. Ingestion of a standard breakfast prior to administration of lovastatin ER tablets decreased absorption of lovastatin by approximately 40%, relative to lovastatin ER tablets under fasting conditions.
Sun
Jim X
JX
Department of Clinical Research, Andrx Laboratories, Inc., Andrx Corporation, Fort Lauderdale, Florida, USA.
Niecestro
Robert
R
Phillips
Gale
G
Shen
Jason
J
Lukacsko
Peter
P
Friedhoff
Lawrence
L
D000328:Adult; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D018565:Food-Drug Interactions; D006207:Half-Life; D006801:Humans; D008148:Lovastatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D016037:Single-Blind Method
D000924:Anticholesteremic Agents; D003692:Delayed-Action Preparations; D008148:Lovastatin