Effect of the Bile Acid Sequestrant Colesevelam on the Pharmacokinetics of Pioglitazone, Repaglinide, Estrogen Estradiol, Norethindrone, Levothyroxine, and Glyburide

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Abstract
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 AUC0‐t (AUC0–48 for levothyroxine) and Cmax fell outside the no‐effect limits of (80.0%, 125.0%). Concomitant administration of colesevelam had no effect on the AUC0‐t or Cmax of pioglitazone but significantly decreased the AUC0‐t and Cmax of glyburide, levothyroxine, and EE and the Cmax of repaglinide and NET. AUC0‐t and Cmax 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.