Effect of colesevelam HCl on single-dose fenofibrate pharmacokinetics.
OBJECTIVE
The primary aim of this study was to determine whether there is an effect of colesevelam HCl (WelChol; Sankyo Pharma Inc., Parsippany, NJ, USA) on fenofibric acid (active metabolite of fenofibrate, TriCor, Abbott Laboratories, North Chicago, IL, USA) pharmacokinetics following single-dose fenofibrate when colesevelam HCl and fenofibrate are administered concomitantly, or when colesevelam HCl is administered 4 hours following fenofibrate therapy.


METHODS
Thirty healthy volunteers were enrolled in a randomised, open-label, three-way crossover, drug interaction study. Subjects received one of three treatments at each of three dose administration periods: (i) treatment A -- fenofibrate 160 mg plus colesevelam HCl 3750 mg (6 x 625 mg tablets) administered with breakfast; (ii) treatment B -- fenofibrate 160 mg administered with breakfast, followed 4 hours later by colesevelam HCl 3750 mg (6 x 625 mg tablets) administered with lunch; or (iii) treatment C -- fenofibrate 160 mg administered with breakfast. Treatments were separated by a 10-day washout period. Blood samples were collected at predetermined time intervals, both before and after drug administration. Plasma concentrations of fenofibrate and fenofibric acid were measured using a validated liquid chromatography/mass spectroscopy/mass spectroscopy method.


RESULTS
Area under the concentration-time curve (AUC) from time zero to the timepoint of the lowest quantifiable concentration (AUCt), AUC from time zero to infinity (AUCinfinity) and maximum plasma concentration (Cmax) for fenofibric acid were 92.1%, 93.9% and 79.8%, respectively, of control values when colesevelam HCl and fenofibrate were coadministered with breakfast; and 91.9%, 93.9% and 99.1%, respectively, when fenofibrate was administered followed 4 hours later by administration of colesevelam HCl. The 90% confidence intervals for the ratios of geometric means for AUCt, AUCinfinity and Cmax comparing the three treatments were contained within the 80-125% equivalence range, with the exception of Cmax for treatment A. Coadministration of fenofibrate with colesevelam HCl resulted in an approximate 20% reduction in Cmax of the active metabolite (fenofibric acid). There were no significant differences in the time to Cmax, elimination rate constant or elimination half-life between any of the treatment groups.


CONCLUSIONS
Colesevelam HCl had no significant effect on fenofibrate bioavailability when administered either concomitantly with fenofibrate or 4 hours after fenofibrate.
Jones
Michael R
MR
Phase IV Research, Sankyo Pharma Inc., Parsippany, New Jersey, USA. mjones@sankyopharma.com
Baker
Brian A
BA
Mathew
Philip
P
D000328:Adult; D000499:Allylamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019540:Area Under Curve; D000069472:Colesevelam Hydrochloride; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D011345:Fenofibrate / Q000097:blood / Q000493:pharmacokinetics*; D018565:Food-Drug Interactions; D006207:Half-Life; D006801:Humans; D000960:Hypolipidemic Agents / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D013997:Time Factors
D000960:Hypolipidemic Agents; D000499:Allylamine; D000069472:Colesevelam Hydrochloride; D011345:Fenofibrate