Effect of Steady-State Atorvastatin on the Pharmacokinetics of a Single Dose of Colchicine in Healthy Adults Under Fasted Conditions

Background and Objective Colchicine is commonly prescribed for gout. While minimally metabolized by the cytochrome P450 (CYP) 3A4 isoenzyme, colchicine is a substrate for P-glycoprotein (P-gp). Atorvastatin is metabolized primarily by CYP3A4 and is a P-gp inhibitor. Patients with gout often have dyslipidemia; therefore, the potential for co-administration of atorvastatin and colchicine exists. The objective of this study was to determine the effect of oral atorvastatin on the pharmacokinetics of a single, oral dose of colchicine. Methods Twenty-four healthy adult subjects were enrolled in this single-center, open-label, non-randomized, one-sequence, two-period drug–drug interaction study. On day 1, subjects received a single oral dose of colchicine 0.6 mg. After a 14-day washout, subjects received atorvastatin 40 mg once daily for 14 days followed by a single dose of colchicine 0.6 mg co-administered with atorvastatin 40 mg on day 28. Main outcome measures were colchicine maximum plasma concentration ( C max ), area under the plasma concentration–time curve (AUC) from time zero to the last measurable concentration (AUC last ), and AUC from time zero to infinity (AUC ∞ ), which were compared with and without concurrent atorvastatin. Results Colchicine AUC last , AUC ∞, and C max increased by 27, 24, and 31 %, respectively, when co-administered with atorvastatin. Corresponding 90 % confidence intervals around the ratios were outside the established no-effect 80–125 % interval. Conclusion Increased colchicine exposure was observed after a single dose of colchicine was administered with steady-state atorvastatin. Additional studies with multiple dosing of both drugs are needed to further determine the clinical implications of these results.