Method: In this open-label, parallel-group study, 8 subjects in each group were randomized, based on Creatinine Clearance (CrCl), to receive a single dose of oral Col 0.6 mg as follows:
Healthy normal (CrCl> 90 mL/min), mild decrease renal function (CrCl >50 – 90 mL/min), moderate decrease renal function (CrCl >30 – 50 mL/min), severe decrease renal function (CrCl >15 – 30 mL/min), and end-stage renal disease (ESRD) (on and off dialysis, separated by 14 days) CrCl not determined.
Result: Col PK parameters were similar for subjects with normal renal function, subjects with mild renal impairment, and ESRD patients on and off dialysis. However, in subjects with moderate and severe renal impairment, Col clearance was reduced, resulting in higher AUC (approximately 2-fold increase) and Cmax (up to 1.5-fold increase). The single-dose data were then used to predict steady state (10 days) concentrations of Col following the recommended colchicine 0.6 mg twice daily regimen. With twice-daily dosing to steady state, Col concentrations in normal subjects, those with mild decrease, and those in ESRD averaged ~2 ng/mL. These concentrations were greatly exceeded in patients with moderate and severe renal impairment (Col concentrations ~5-6 ng/mL), suggesting that these groups require dosage adjustment.
Despite the reduced clearance of Col in renally impaired subjects, there was no difference in accumulation of metabolites in patients with moderate and severe renal impairment compared to the other groups.
ESRD and dialysis
On the day of dialysis, subjects were given Col 0.6 mg and dialyzed for 3-4 hrs beginning at one-hour post-dose. While on dialysis, the concentrations were generally lower by approximately 0.5 ng/mL.
Conclusion: Based on these data, for the prophylaxis of gout flares, no dosing adjustments are needed for patients with normal renal function or mild impairment (CrCl >50 mL/min) or ESRD on or off hemodialysis. For patients with moderate and severe renal failure (CrCl <50 mL/min), it is recommended that Col dose be reduced 50% (i.e. for those patients requiring 0.6 mg twice daily, the dose should be decreased to 0.6 mg once a day, and for those requiring 0.6 mg once a day, the dose should be decreased to 0.3 mg per day).
Disclosure: S. Wason, URL Pharma, 3 ; R. D. Faulkner, URL Pharma, 3 ; M. W. Davis, URL Pharma, 3 .