title: The effects of colesevelam HCl on the single-dose pharmacokinetics of glimepiride, extended-release glipizide, and olmesartan medoxomil.
abstract: Bile acid sequestrants can potentially bind to concomitant drugs. Single-dose studies evaluated the effects of colesevelam on the pharmacokinetics of glimepiride, glipizide extended-release (ER), and olmesartan medoxomil. Each study enrolled healthy subjects aged 18-45 years. The olmesartan medoxomil study used a randomized adaptive crossover design that initially compared olmesartan medoxomil alone versus simultaneously with colesevelam, then olmesartan medoxomil alone versus 4 hours before colesevelam. The other studies used a three-period crossover design (test drug alone, test drug simultaneously with colesevelam, and test drug 4 hours before colesevelam). For the colesevelam coadministration periods, 3,750 mg once daily was dosed throughout the pharmacokinetic sampling period. After each single dose of test drug, serial blood samples were collected for determination of plasma drug concentrations and calculation of pharmacokinetic parameters. Administering colesevelam simultaneously with glimepiride or glipizide ER resulted in minor reductions (18% and 13%, respectively) in total exposure that were negated by staggering colesevelam dosing by 4 hours. Administering colesevelam simultaneously with olmesartan medoxomil resulted in a major reduction (39%) in olmesartan exposure that was reduced by staggering colesevelam dosing by 4 hours. This reduction in olmesartan exposure is not predicted to have a clinically significant impact on blood pressure control.
authors.affiliation: Daiichi Sankyo Pharma Development, Edison, NJ, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: He
authors.forename: Prachi
authors.initials: P
authors.lastname: Wickremasingha
authors.forename: James
authors.initials: J
authors.lastname: Lee
authors.forename: Ben
authors.initials: B
authors.lastname: Tao
authors.forename: Jeanne
authors.initials: J
authors.lastname: Mendell-Harary
authors.forename: Joseph
authors.initials: J
authors.lastname: Walker
authors.forename: Douglas
authors.initials: D
authors.lastname: Wight
mesh_terms: D000328:Adult; D000465:Algorithms; D000499:Allylamine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000493:pharmacokinetics*; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000494:pharmacology*; D019540:Area Under Curve; D000069472:Colesevelam Hydrochloride; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004347:Drug Interactions; D005260:Female; D005913:Glipizide / Q000009:adverse effects / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D007093:Imidazoles / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D000068557:Olmesartan Medoxomil; D013453:Sulfonylurea Compounds / Q000009:adverse effects / Q000493:pharmacokinetics*; D013777:Tetrazoles / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000924:Anticholesteremic Agents; D003692:Delayed-Action Preparations; D007004:Hypoglycemic Agents; D007093:Imidazoles; D013453:Sulfonylurea Compounds; D013777:Tetrazoles; D000499:Allylamine; C057619:glimepiride; D000068557:Olmesartan Medoxomil; D000069472:Colesevelam Hydrochloride; D005913:Glipizide
keywords: colesevelam; drug-drug interactions; glimepiride; glipizide; olmesartan medoxomil