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Single-Dose, Open-Label Study of the Differences in Pharmacokinetics of Colchicine in Subjects with Renal Impairment, Including End-Stage Renal Disease

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Abstract

Background and Objective

The effect of renal impairment on colchicine pharmacokinetics in patients with chronic kidney disease (CKD) has not been studied previously. We evaluated the effect of renal impairment on colchicine pharmacokinetics in patients with CKD.

Methods

The pharmacokinetics and safety of a single, oral 0.6-mg dose of colchicine was evaluated in an open-label study in eight healthy subjects with normal renal function; eight subjects each with mild, moderate, or severe renal impairment; and eight subjects with end-stage renal disease (ESRD) who received a single dose prior to receiving, and again following, hemodialysis.

Results

Colchicine exposure was similar for subjects with normal renal function, mild impairment, or ESRD prior to and during hemodialysis (24.7–31.7 ng·h/mL), but was up to twofold higher in subjects with moderate or severe renal impairment (48.9 and 48.0 ng·h/mL, respectively). A very small amount of the colchicine dose (mean of 5.2 %) was recovered in dialysate.

Conclusions

It appears that patients with mild or moderate renal impairment or those actively receiving hemodialysis do not show accumulation of colchicine, whereas those with severe renal impairment show a doubling of exposure. All patients with renal impairment taking colchicine should be closely monitored, especially as many patients taking colchicine often have other comorbidities and may be taking other medications.

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Acknowledgments

Initial editorial assistance in the preparation of this manuscript was provided by Peter Todd, PhD, and James A. Shiffer, RPh, of Write On Time Medical Communications, LLC, who received original financial support from URL Pharma, Inc., (Philadelphia, PA, USA). Additional writing and editorial assistance was provided by Courtney Mezzacappa Zeni, PhD, and Meryl Gersh, PhD, of AlphaBioCom, LLC (King of Prussia, PA, USA) and was supported by Takeda Pharmaceuticals International, Inc., Deerfield, IL, USA.

Conflicts of interest

This study was sponsored by Mutual Pharmaceutical Company, Inc. (now part of Takeda Pharmaceuticals U.S.A., Inc., Deerfield, IL, USA). At the time of this study, Suman Wason was an employee of Mutual Pharmaceutical Company, Inc., and was part of the Takeda Pharmaceuticals U.S.A., Inc. family of companies. Robert Faulkner is a URL Pharma employee. David Mount has no financial conflicts of interest to declare.

Author information

Author notes

  1. Robert Faulkner

    Present address: URL Pharma, Inc., 1100 Orthodox Street, Philadelphia, PA, 19124, USA

  2. Suman Wason

    Present address: Lexicon Pharmaceuticals, Inc., 8800 Technology Forest Pl, The Woodlands, TX, 77381, USA

Authors and Affiliations

  1. Mutual Pharmaceutical Company, Inc., Philadelphia, PA, 19124, USA

    Suman Wason & Robert Faulkner

  2. Renal Division, Brigham and Women’s Hospital, Harvard Institutes of Medicine, Room 542, 4 Blackfan Circle, Boston, MA, USA

    David Mount

  3. Renal Division, VA Boston Healthcare System, Room B7-57, 150 S. Huntington Avenue, Boston, MA, USA

    David Mount

Authors
  1. Suman Wason
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  2. David Mount
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  3. Robert Faulkner
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Corresponding author

Correspondence to Robert Faulkner.

Additional information

Robert Faulkner and Suman Wason were working with Mutual Pharmaceutical Company, Inc., Philadelphia, PA, 19124, USA at the time of the study (now part of Takeda Pharmaceuticals U.S.A., Inc., Deerfield, IL, USA).

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Wason, S., Mount, D. & Faulkner, R. Single-Dose, Open-Label Study of the Differences in Pharmacokinetics of Colchicine in Subjects with Renal Impairment, Including End-Stage Renal Disease. Clin Drug Investig 34, 845–855 (2014). https://doi.org/10.1007/s40261-014-0238-6

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  • DOI: https://doi.org/10.1007/s40261-014-0238-6

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