The comparative bioavailability of an extended-release niacin and lovastatin fixed dose combination tablet versus extended-release niacin tablet, lovastatin tablet and a combination of extended-release niacin tablet and lovastatin tablet

Abstract

Lovastatin and extended-release (ER) niacin in a fixed dose combination (Advicor^®) is approved for the treatment of dyslipidemia. Since both drugs are extensively metabolized, this study investigated the bioavailability and pharmacokinetics of their co-administration following single-dose administration. In a 4-way crossover study 40 subjects received: two 1000/20 Advicor tablets (ADV), two 1000mg niacin ER tablets (NSP), two 20mg lovastatin tablets (Mevacor^®; MEV), and two niacin ER 1000mg tablets with two lovastatin 20mg tablets (NSP+MEV). Plasma was assayed for niacin, nicotinuric acid (NUA), lovastatin, lovastatin acid and HMGCoA reductase inhibition. Urine was assayed for niacin and its metabolites, NUA, N-methylnicotinamide and N-methyl-2pyridone-5-carboxamide. Least square mean ratios and 90% confidence intervals for C_max and AUC_(0−t) were determined for NSP+MEV versus MEV or NSP, ADV versus MEV or NSP, and ADV versus NSP+MEV. Co-administration of niacin and lovastatin did not significantly influence C_max and AUC_(0−t) of lovastatin, niacin, NUA and total urinary recovery of niacin and metabolites. A 22 to 25% decrease in lovastatin acid C_max was observed while lovastatin acid AUC_(0−t) was not affected. The HMGCoA reductase inhibition C_max and AUC_(0−t) were not affected indicating that the difference in lovastatin acid C_max was not clinically relevant. Copyright © 2007 John Wiley & Sons, Ltd.