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

Colesevelam hydrochloride (colesevelam) is a novel, potent, bile acid-bindi ng agent that has been shown to lower LDL cholesterol a mean of 19% at a do se of 3.8 g/d. me studied the pharmacokinetics of colesevelam coadministere d with six drugs: digoxin and warfarin, agents with narrow therapeutic indi ces; sustained-release verapamil and metoprolol; quinidine, an antiarrhythm ic with a narrow therapeutic index; and valproic acid, an antiseizure medit ation. Six individual studies were single-dose, crossover, with or without a 4.5-g dose of colesevelam. plasma levels mere determined using validated analytical methods. Values for the ratio of 1n[AUC(0-t)] with and without c olesevelam were 107% for quinidine, 102% far valproic acid, 89% for digoxin , 102% for warfarin, 82% for verapamil, and 112% for metoprolol. Values for the ratio of 1n[C-max]with and without colesevelam were 107% for quinidine , 92% for valproic acid, 96% for digoxin, 99% for warfarin, 69% for verapam il, and 112% for metoprolol. The 90% confidence intervals for these ratios and for values of 1n[AUC(0-inf)] that could be determined were within the 8 0-125% range, with the exception of verapamil. In this study, verapamil had great interindividual variability, with a 28-fold range in C-max and an 11 -fold range in AUC(0-t). In summary, pharmacokinetic studies with colesevel am did not show clinically significant effects on absorption of six other c oadministered drugs.