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 1000 mg niacin ER tablets (NSP), two 20mg lovastatin tablets (Mevacor; MEV), and two niacin ER 1000 mg 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.

• Authors: R Menon, D Tolbert, E Cefali
• Journal: Biopharmaceutics & drug disposition (Biopharm Drug Dispos) Vol. 28 Issue 6 Pg. 297-306 (Sep 2007) ISSN: 0142-2782 [Print] England
• PMID: 17571283 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial)

Chemical References

• Antineoplastic Agents
• Delayed-Action Preparations
• Drug Combinations
• N-methyl-2-pyridone-5-carboxamide
• Nicotinic Acids
• Pyridones
• Tablets
• Vitamin B Complex
• Niacinamide
• Niacin
• nicotinuric acid
• Lovastatin
• N-methylnicotinamide

Topics

• Adult
• Aged
• Antineoplastic Agents (metabolism, pharmacokinetics)
• Area Under Curve
• Biological Availability
• Cross-Over Studies
• Delayed-Action Preparations (adverse effects, pharmacokinetics)
• Drug Combinations
• Female
• Flushing (chemically induced)
• Humans
• Lovastatin (blood, pharmacokinetics, urine)
• Male
• Metabolic Clearance Rate
• Middle Aged
• Nausea (chemically induced)
• Niacin (blood, pharmacokinetics, urine)
• Niacinamide (analogs & derivatives, metabolism)
• Nicotinic Acids (metabolism)
• Pyridones (urine)
• Tablets
• Time Factors
• Vitamin B Complex (blood, pharmacokinetics, urine)