Introduction: The objective of this study was to compare the relative bioavailability of the US Food and Drug Administration-approved formulation of colchicine after a single 0.6 mg dose in young (18-30 years of age) and elderly (≥60 years of age) healthy subjects to determine whether dosing adjustments are required in elderly patients.
Methods: A single-dose, single-drug, parallel-group study was performed in 20 young subjects with normal renal function (defined as creatinine clearance [CrCl] ≥80 mL/min) and 18 elderly subjects with normal or mild renal impairment (CrCl ≥50 mL/min) in otherwise good health. Blood samples were collected for up to 72 hours postdose and analyzed for colchicine using a validated liquid chromatography/tandem mass spectrometry method. Noncompartmental pharmacokinetic parameters were compared using analysis of variance methods.
Results: There were no statistically significant (P < 0.05) differences in mean colchicine pharmacokinetic parameters between young and elderly subjects, including peak plasma concentration (C(max)) (2.53 vs. 2.56 ng/mL), time to C(max) (1.25 vs. 1.25 hours), area under the plasma concentration-time curve to infinity (22.29 vs. 25.01 ng/h/mL), elimination half-life (25.4 vs. 30.1 hours), oral clearance (0.40 vs. 0.35 L/h/kg), and apparent volume of distribution (14.3 vs. 14.8 L/kg), respectively.
Conclusion: The lack of any significant differences in colchicine pharmacokinetic parameters between young and elderly healthy subjects, with some of the latter including mild renal impairment, suggests that dose modification of colchicine may not be necessary in healthy elderly patients. However, when evaluating the use of colchicine dosing in an elderly patient, the confounding effect on overall exposure and safety from comorbid conditions, the use of concomitant medications, and the administration of multiple doses should be considered.