Drug interactions with colesevelam hydrochloride, a novel, potent lipid-lowering agent

Cardiovasc Drugs Ther. 2000 Dec;14(6):681-90. doi: 10.1023/a:1007831418308.


Colesevelam hydrochloride (colesevelam) is a novel, potent, bile acid-binding agent that has been shown to lower LDL cholesterol a mean of 19% at a dose of 3.8 g/d. We studied the pharmacokinetics of colesevelam coadministered with six drugs: digoxin and warfarin, agents with narrow therapeutic indices; sustained-release verapamil and metoprolol; quinidine, an antiarrhythmic with a narrow therapeutic index; and valproic acid, an antiseizure medication. Six individual studies were single-dose, crossover, with or without a 4.5-g dose of colesevelam. Plasma levels were determined using validated analytical methods. Values for the ratio of ln[AUC(0-t)] with and without colesevelam were 107% for quinidine, 102% for valproic acid, 89% for digoxin, 102% for warfarin, 82% for verapamil, and 112% for metoprolol. Values for the ratio of ln[Cmax] with and without colesevelam were 107% for quinidine, 92% for valproic acid, 96% for digoxin, 99% for warfarin, 69% for verapamil, and 112% for metoprolol. The 90% confidence intervals for these ratios and for values of ln[AUC(0-inf)] that could be determined were within the 80-125% range, with the exception of verapamil. In this study, verapamil had great interindividual variability, with a 28-fold range in Cmax and an 11-fold range in AUC(0-t). In summary, pharmacokinetic studies with colesevelam did not show clinically significant effects on absorption of six other coadministered drugs.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allylamine / analogs & derivatives
  • Allylamine / pharmacology*
  • Anticholesteremic Agents / pharmacology*
  • Area Under Curve
  • Cardiovascular Agents / pharmacokinetics*
  • Colesevelam Hydrochloride
  • Drug Interactions
  • Female
  • Half-Life
  • Humans
  • Intestinal Absorption / drug effects
  • Male


  • Anticholesteremic Agents
  • Cardiovascular Agents
  • Allylamine
  • Colesevelam Hydrochloride