Lack of effect of colesevelam HCl on the single-dose pharmacokinetics of aspirin, atenolol, enalapril, phenytoin, rosiglitazone, and sitagliptin.
OBJECTIVE
Drug interactions with bile acid sequestrants are primarily due to the potential of these agents to bind to concomitant drugs. Six clinical studies were performed to determine the effects of colesevelam on the pharmacokinetics of aspirin, atenolol, enalapril, phenytoin, rosiglitazone, and sitagliptin.


METHODS
All six studies enrolled healthy subjects aged 18-45 years. The phenytoin study used a single-dose, three-period crossover design (phenytoin alone, phenytoin simultaneously with colesevelam, and phenytoin 4h before colesevelam). The other studies used a two-period crossover design (test drug alone and test drug simultaneously with colesevelam). Colesevelam (3750mg once daily) was dosed throughout the pharmacokinetic sampling period. After each single dose of the test drug, serial blood samples were collected for determination of plasma drug concentrations and calculation of pharmacokinetic parameters.


RESULTS
For all six test drugs, 90% CIs for geometric least-squares mean ratios of AUC and Cmax for the measured analytes were within specified limits, indicating no interaction between the test drug and colesevelam.


CONCLUSIONS
Aspirin, atenolol, enalapril, rosiglitazone, and sitagliptin may be taken with colesevelam. Although the phenytoin study indicated no pharmacokinetic interaction, phenytoin should continue to be taken ≥4h before colesevelam in accordance with current prescribing information.
Daiichi Sankyo Pharma Development, Edison, NJ, USA. Electronic address: lhe@dsi.com.
Ling
L
He
Daiichi Sankyo Pharma Development, Edison, NJ, USA.
Prachi
P
Wickremasingha
Daiichi Sankyo Pharma Development, Edison, NJ, USA.
James
J
Lee
Daiichi Sankyo Pharma Development, Edison, NJ, USA.
Ben
B
Tao
Daiichi Sankyo Pharma Development, Edison, NJ, USA.
Jeanne
J
Mendell-Harary
Daiichi Sankyo Pharma Development, Edison, NJ, USA.
Joseph
J
Walker
Milestone Pharmaceuticals, Montreal, Québec, Canada.
Douglas
D
Wight
D000293:Adolescent; D000328:Adult; D000499:Allylamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics; D000924:Anticholesteremic Agents / Q000494:pharmacology; D000927:Anticonvulsants / Q000493:pharmacokinetics; D000959:Antihypertensive Agents / Q000493:pharmacokinetics; D019540:Area Under Curve; D001241:Aspirin / Q000493:pharmacokinetics*; D001262:Atenolol / Q000493:pharmacokinetics*; D000069472:Colesevelam Hydrochloride; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004656:Enalapril / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D010672:Phenytoin / Q000493:pharmacokinetics*; D011719:Pyrazines / Q000493:pharmacokinetics*; D000077154:Rosiglitazone; D000068900:Sitagliptin Phosphate; D045162:Thiazolidinediones / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014230:Triazoles / Q000493:pharmacokinetics*; D055815:Young Adult
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000924:Anticholesteremic Agents; D000927:Anticonvulsants; D000959:Antihypertensive Agents; D007004:Hypoglycemic Agents; D011719:Pyrazines; D045162:Thiazolidinediones; D014230:Triazoles; D000077154:Rosiglitazone; D000499:Allylamine; D001262:Atenolol; D010672:Phenytoin; D004656:Enalapril; D000069472:Colesevelam Hydrochloride; D001241:Aspirin; D000068900:Sitagliptin Phosphate
Anticonvulsants; Antihypertensive agents; Colesevelam; Drug–drug interactions; Hypoglycemic agents