Effect of the bile acid sequestrant colesevelam on the pharmacokinetics of pioglitazone, repaglinide, estrogen estradiol, norethindrone, levothyroxine, and glyburide.
The purpose of this study was to assess effects of colesevelam on the pharmacokinetics of glyburide, levothyroxine, estrogen estradiol (EE), norethindrone (NET), pioglitazone, and repaglinide in healthy volunteers. Six drugs with a potential to interact with colesevelam were studied in open-label, randomized clinical studies. The presence of a drug interaction was concluded if the 90% confidence intervals for the geometric least squares mean ratios of AUC(0-t) (AUC(0-48) for levothyroxine) and C(max) fell outside the no-effect limits of (80.0%, 125.0%). Concomitant administration of colesevelam had no effect on the AUC(0-t) or C(max) of pioglitazone but significantly decreased the AUC(0-t) and C(max) of glyburide, levothyroxine, and EE and the C(max) of repaglinide and NET. AUC(0-t) and C(max) of glyburide and EE, but not repaglinide or NET, were significantly decreased when the drug was given 1 hour before colesevelam. When glyburide, EE, or levothyroxine was given 4 hours before colesevelam, no drug interaction was observed. Although colesevelam has a cleaner drug interaction profile than other bile acid sequestrants, it does interfere with absorption of some drugs. A 4-hour window appears sufficient to eliminate these interactions.
Brown
Karen S
KS
Daiichi Sankyo Pharma Development, 399 Thornall Street, Edison, NJ 08837, USA. kbrown@dsus.com
Armstrong
Ingrid C
IC
Wang
Antonia
A
Walker
Joseph R
JR
Noveck
Robert J
RJ
Swearingen
Dennis
D
Allison
Mark
M
Kissling
James C
JC
Kisicki
James
J
Salazar
Daniel E
DE
D000499:Allylamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D019540:Area Under Curve; D000069472:Colesevelam Hydrochloride; D003277:Contraceptives, Oral, Combined / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics; D016018:Least-Squares Analysis; D008297:Male; D013974:Thyroxine / Q000493:pharmacokinetics; D013997:Time Factors
D000924:Anticholesteremic Agents; D003277:Contraceptives, Oral, Combined; D007004:Hypoglycemic Agents; D000499:Allylamine; D000069472:Colesevelam Hydrochloride; D013974:Thyroxine