Oral Absorption Characteristics and Pharmacokinetics of Colchicine in Healthy Volunteers after Single and Multiple Doses

Abstract

Colchicine is an antimitotic drug used to treat gout and familial Mediterranean fever. Absolute bioavailability, pharmacokinetics, and absorption characteristics of colchicine after single 1.0-mg doses in oral solution or tablet form or 0.5-mg intravenous doses were compared in 6 subjects. This study was combined with 14 days of multiple-dose administration of 1.0-mg colchicine tablets in 6 subjects. Serial blood samples were collected for 48 hours after administration of single doses and for 120 hours after the last dose in the multiple-dose regimen. Plasma colchicine profiles as measured by radioimmunoassay were analyzed using deconvolution and compartmental methods. After intravenous bolus injection of colchicine, the area under the concentration-time curve (AUC) was 61.2 ± 12.7 ng · hr/mL, steady-state volume of distribution (V₈₈) was 419 ± 95 L, systemic clearance (Cl) was 8.5 ± 1.8 L/hr, and the terminal half-life (t_1/2) was 57.8 ± 10.7 hours. After oral administration in solution form, peak plasma concentrations (C_max) of 6.50 ± 1.03 ng/mL were reached at time (t_max) 1.07 ± 0.55 hours, with a rate of 0.109 ± 0.024 hr⁻¹ (C_max/AUC); bioavailability was 47 ± 14%. Oral tablets yielded similar C_max, t_max, and C_max/AUC values, but AUC was significantly lower. Most participants exhibited a secondary peak within 6 hours of administration, possibly in relation to a second absorption site or enterohepatic recirculation. This second absorption process was significantly longer than the first one, and accounted for a similar amount of colchicine absorbed. From the multiple-dose study, a model including an alteration of colchicine absorption due to possible drug-induced gastrointestinal modifications allowed better determination of steady-state plasma concentrations of colchicine.