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

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 Cmax 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 Cmax and AUC(0−t) of lovastatin, niacin, NUA and total urinary recovery of niacin and metabolites. A 22 to 25% decrease in lovastatin acid Cmax was observed while lovastatin acid AUC(0−t) was not affected. The HMGCoA reductase inhibition Cmax and AUC(0−t) were not affected indicating that the difference in lovastatin acid Cmax was not clinically relevant. Copyright © 2007 John Wiley & Sons, Ltd.