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Effect of the Bile Acid Sequestrant Colesevelam on the Pharmacokinetics of Pioglitazone, Repaglinide, Estrogen Estradiol, Norethindrone, Levothyroxine, and Glyburide
Author(s) -
Brown Karen S.,
Armstrong Ingrid C.,
Wang Antonia,
Walker Joseph R.,
Noveck Robert J.,
Swearingen Dennis,
Allison Mark,
Kissling James C.,
Kisicki James,
Salazar Daniel E.
Publication year - 2010
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270009349378
Subject(s) - repaglinide , pioglitazone , medicine , levothyroxine , pharmacokinetics , endocrinology , drug interaction , pharmacology , insulin , diabetes mellitus , type 2 diabetes , hormone , metformin
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.