Differences in metabolism of time-release and unmodified nicotinic acid: explanation of the differences in hypolipidemic action?

Metabolism. 1992 Aug;41(8):879-81. doi: 10.1016/0026-0495(92)90170-f.


The possibility that differences in metabolism might underly the differences in efficacy and toxicity between time-release and unmodified formulations of nicotinic acid was investigated by measuring 24-hour urinary excretion of metabolites in 10 subjects who received both forms. Nicotinic acid has two metabolic fates: formation of nicotinamide adenine dinucleotide (NAD) and formation of nicotinuric acid, the glycine conjugate of nicotinic acid. Catabolism of NAD releases nicotinamide, which is subsequently methylated and/or oxidized to form a number of metabolites, with 2-pyridone predominating. Excretion of nicotinuric acid was more than four times greater when subjects took unmodified nicotinic acid than when they took time-release nicotinic acid (78.2 and 18.8 mg, respectively). In contrast, excretion of 2-pyridone with unmodified nicotinic acid was only 30% more than with time-release nicotinic acid (171.0 and 129.9 mg, respectively). These results demonstrate a marked difference in the metabolism of unmodified and time-release nicotinic acid. It is proposed that nicotinyl coenzyme A (CoA), the metabolic intermediate in the formation of nicotinuric acid, mediates some of the hypolipidemic actions of nicotinic acid, as the acyl-CoA esters of xenobiotics, including clofibrate, have been shown to interfere with lipid metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Delayed-Action Preparations
  • Humans
  • Lipids / blood*
  • Male
  • Niacin / pharmacokinetics*
  • Niacin / urine
  • Nicotinic Acids / urine
  • Pyridones / urine


  • Delayed-Action Preparations
  • Lipids
  • Nicotinic Acids
  • Pyridones
  • Niacin
  • nicotinuric acid