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 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.
Menon
R
R
Kos Pharmaceuticals Inc, Weston, FL 33326, USA. menonrm2000@yahoo.com
Tolbert
D
D
Cefali
E
E
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000378:metabolism / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000009:adverse effects / Q000493:pharmacokinetics*; D004338:Drug Combinations; D005260:Female; D005483:Flushing / Q000139:chemically induced; D006801:Humans; D008148:Lovastatin / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009525:Niacin / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D009536:Niacinamide / Q000031:analogs & derivatives / Q000378:metabolism; D009539:Nicotinic Acids / Q000378:metabolism; D011728:Pyridones / Q000652:urine; D013607:Tablets; D013997:Time Factors; D014803:Vitamin B Complex / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004338:Drug Combinations; C525085:N-methyl-2-pyridone-5-carboxamide; D009539:Nicotinic Acids; D011728:Pyridones; D013607:Tablets; D014803:Vitamin B Complex; D009536:Niacinamide; D009525:Niacin; C002477:nicotinuric acid; D008148:Lovastatin; C008472:N-methylnicotinamide