caa a22 4500 475833384 CHVBK 20180406123847.0 cr unu---uuuuu 170329e20001201xx s 000 0 eng 10.1023/A:1007831418308 doi (NATIONALLICENCE)springer-10.1023/A:1007831418308 Drug Interactions with Colesevelam Hydrochloride, a Novel, Potent Lipid-Lowering Agent [Elektronische Daten] [Joanne Donovan, Daria Stypinski, Mark Stiles, Timothy Olson, Steven Burke] 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. Kluwer Academic Publishers, 2000 colesevelam hydrochloride nationallicence bile acid sequestrant nationallicence drug interactions nationallicence pharmacokinetics nationallicence digoxin nationallicence warfarin nationallicence quinidine nationallicence verapamil nationallicence metoprolol nationallicence valproic acid nationallicence Donovan Joanne GelTex Pharmaceuticals, Waltham, Massachusetts, Nebraska, USA aut Stypinski Daria MDS Harris, Lincoln, Nebraska, USA aut Stiles Mark MDS Harris, Lincoln, Nebraska, USA aut Olson Timothy GelTex Pharmaceuticals, Waltham, Massachusetts, Nebraska, USA aut Burke Steven GelTex Pharmaceuticals, Waltham, Massachusetts, Nebraska, USA aut Cardiovascular Drugs and Therapy Kluwer Academic Publishers 14/6(2000-12-01), 681-690 0920-3206 14:6<681 2000 14 10557 https://doi.org/10.1023/A:1007831418308 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1007831418308 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Donovan Joanne GelTex Pharmaceuticals, Waltham, Massachusetts, Nebraska, USA aut NATIONALLICENCE 700 1- Stypinski Daria MDS Harris, Lincoln, Nebraska, USA aut NATIONALLICENCE 700 1- Stiles Mark MDS Harris, Lincoln, Nebraska, USA aut NATIONALLICENCE 700 1- Olson Timothy GelTex Pharmaceuticals, Waltham, Massachusetts, Nebraska, USA aut NATIONALLICENCE 700 1- Burke Steven GelTex Pharmaceuticals, Waltham, Massachusetts, Nebraska, USA aut NATIONALLICENCE 773 0- Cardiovascular Drugs and Therapy Kluwer Academic Publishers 14/6(2000-12-01), 681-690 0920-3206 14:6<681 2000 14 10557 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer