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Effect of Colesevelam HCl on Single-Dose Fenofibrate Pharmacokinetics

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Abstract

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 160mg plus colesevelam HCl 3750mg (6 × 625mg tablets) administered with breakfast; (ii) treatment B - fenofibrate 160mg administered with breakfast, followed 4 hours later by colesevelam HC1 3750mg (6 × 625mg tablets) administered with lunch; or (iii) treatment C - fenofibrate 160mg 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 (AUC∞) and maximum plasma concentration (Cmax) for fenofibric acid were 92.1%, 93.9% and 79.8%, respectively, of control values when colesevelam HC1 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 HC1. The 90% confidence intervals for the ratios of geometric means for AUCt, AUC∞ 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.

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Table I

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

  2. Coadministration of ezetimibe with fibrates is not recommended as the safety and effectiveness of this combination has not been established at this time.

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Acknowledgements

This study was funded by Sankyo Pharma Inc. Drs Jones and Baker are employed by Sankyo Pharma Inc. Dr Mathew is employed by the Sankyo Clinical Pharmacology Unit, MDS Pharma Services.

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Authors and Affiliations

  1. Phase IV Research, Sankyo Pharma Inc., Two Hilton Court, Parsippany, New Jersey, 07054, USA

    Michael R. Jones

  2. Medical and Scientific Affairs, Sankyo Pharma Inc., Parsippany, New Jersey, USA

    Brian A. Baker

  3. Sankyo Clinical Pharmacology Unit, MDS Pharma Services, Neptune, New Jersey, USA

    Philip Mathew

Authors
  1. Michael R. Jones
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  2. Brian A. Baker
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  3. Philip Mathew
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Correspondence to Michael R. Jones.

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Jones, M.R., Baker, B.A. & Mathew, P. Effect of Colesevelam HCl on Single-Dose Fenofibrate Pharmacokinetics. Clin Pharmacokinet 43, 943–950 (2004). https://doi.org/10.2165/00003088-200443130-00006

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