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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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.
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.
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.
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.
KeywordsChronic Kidney Disease Renal Impairment Colchicine Gout Familial Mediterranean Fever
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.
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