Pharmacokinetics and absolute bioavailability of colchicine after i. v. and oral administration in healthy human volunteers and elderly subjects

Abstract

The pharmacokinetics of colchicine were studied in six healthy male and four elderly female volunteers after i. v. and oral administration. Plasma samples were collected over 72 h and assayed for colchicine by a specific and sensitive radioimmunoassay. Plasma concentration-time curves were fitted using a three-compartmental model after i. v. administration of 0.5 mg (healthy volunteers) and 1 mg (elderly group) colchicine. The first distribution half-life (t_1/2 λ₁) was short: 9.2 min in healthy volunteers and 3.0 min in the elderly group; the second distribution half-life (t_1/2 λ₂) was of the same order for both groups, 1.2 h. Plasma elimination half-lives were also in the same range: 30 h for healthy volunteers versus 34 h for the elderly subjects. Mean residence time was also in the same range in the two groups: 27 h in healthy volunteers and 21 h for elderly subjects. The volume of distribution (V_z) was 6.71·kg^-1 for the healthy group and 6.31·kg^-1 for the elderly group, while V_ss was smaller: 4.21·kg^-1 for healthy volunteers and 2.91·kg^-1 for elderly subjects. Total body clearance was 10.51·h^-1 for healthy and 5.51·h^-1 for elderly subjects.

After oral administration of 1 mg, lag-time was 14 min in healthy volunteers and 11 min in elderly subjects. Maximal plasma concentration was 5.5 ng·ml^-1 at 62 min in the healthy group, while in the elderly group C_max was 12 ng·ml^-1 at 87 min. Mean absolute bioavailability of the tablet was the same in both groups, 44% for healthy volunteers and 45% for elderly subjects.