Pharmacokinetics and bioequivalence study of two tablet formulations of lovastatin in healthy volunteers.
Lovastatin is a lipid-lowering agent indicated for primary hypercholesterolemia. This study has assessed single-dosing pharmacokinetics of lovastatin and of its main metabolite, lovastatin beta-hydroxyacid, and has compared the pharmacokinetics of two formulations of lovastatin, a test lovastatin generic (LVSG), and a reference (mevinacor 40 MSD) preparation. The pharmacokinetics and bioequivalence of the two formulations of lovastatin were evaluated by a two-way cross-over randomized double blinded study, in 36 healthy volunteers after a single oral dose of 2 x 40 mg per subject. On plasma samples, collected at given intervals of time (0-24h), lovastatin and its main active metabolite were assayed by high pressure liquid chromatography with positive turbo ion spray ionization tandem mass spectrometry detection. The pharmacokinetic parameters, area under the curve total (AUC(t)) and to infinity (AUC(inf)), peak plasma concentration (C(max)), time to attain peak (t(max)), and elimination half-life (t(1/2)) were determined and analyzed statistically. Only minor differences in the pharmacokinetics of lovastatin and lovastatin hydroxyacid between LVSG and mevinacor were found. Analysis of variance (ANOVA) did not show any significant difference between the two formulations, and 90% confidence intervals fell within the acceptable range for bioequivalence. The tolerability profile was good and comparable for the two formulations of lovastatin. Our study, which was performed with the largest number of subjects compared with those published in literature, indicates the bioequivalence of LVSG and mevinacor tablets. The high inter-subject variability of parameters investigated indicate the need of appropriate sample size in pharmacokinetics studies with lovastatin.
Mignini
Fiorenzo
F
Centro di Ricerche Cliniche, Dipartimento di Medicina Sperimentale e Sanità Pubblica, Università di Camerino, Camerino, Italy.
Tomassoni
Daniele
D
Streccioni
Valentino
V
Traini
Enea
E
Amenta
Francesco
F
D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D016568:Drugs, Generic / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D008148:Lovastatin / Q000009:adverse effects / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D012016:Reference Values; D013607:Tablets; D013810:Therapeutic Equivalency
D016568:Drugs, Generic; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013607:Tablets; D008148:Lovastatin