Document Detail


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.
MedLine Citation:
PMID:  17571283     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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
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Publication Detail:
Type:  Comparative Study; Journal Article; Randomized Controlled Trial    
Journal Detail:
Title:  Biopharmaceutics & drug disposition     Volume:  28     ISSN:  0142-2782     ISO Abbreviation:  Biopharm Drug Dispos     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-08-21     Completed Date:  2007-12-20     Revised Date:  2011-01-14    
Medline Journal Info:
Nlm Unique ID:  7911226     Medline TA:  Biopharm Drug Dispos     Country:  England    
Other Details:
Languages:  eng     Pagination:  297-306     Citation Subset:  IM    
Affiliation:
Kos Pharmaceuticals Inc, Weston, FL 33326, USA. menonrm2000@yahoo.com
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MeSH Terms
Descriptor/Qualifier:
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
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Delayed-Action Preparations; 0/Drug Combinations; 0/N-methyl-2-pyridone-5-carboxamide; 0/Nicotinic Acids; 0/Pyridones; 0/Tablets; 114-33-0/N-methylnicotinamide; 12001-76-2/Vitamin B Complex; 583-08-4/nicotinuric acid; 59-67-6/Niacin; 75330-75-5/Lovastatin; 98-92-0/Niacinamide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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