Abstract
Formulation ingredients may influence the pharmacokinetics of co-administered drugs. We investigated whether oral pre-dosing with the inactive formulation ingredient Solutol affects the pharmacokinetic profile of intravenously administered colchicine in rats. Colchicine was administered intravenously to male Wistar rats as solution in isotonic sodium chloride (NaCl 0.9%, control group) at 1.5 mg/kg. A second group of rats received the intravenous dose of colchicine 20 minutes after oral pre-dosage with 4 mg/kg of a 90:10 (v/v) mixture of NaCl 0.9% and Solutol HS 15 (Solutol). At predetermined time points, plasma and urine were collected from the animals and analyzed for colchicine and its demethylated metabolites by LC/MS-MS. After oral pre-treatment with Solutol, colchicine plasma clearance (Cl) was decreased by a factor of two and its maximum plasma concentration (cmax) was almost twofold increased as compared to the control group. Moreover, the amount of parent colchicine excreted into urine within 24 hours after administration did increase twentyfold in the Solutol treated group. Renal excretion of colchicine metabolites was slightly increased. We conclude that absorption of Solutol and/or its degradation products into the systemic circulation seems to be a major contributor to the observed effects. Our results suggest that oral administration of formulation ingredients may alter the distribution kinetics of drugs, which are co-administered orally as well as intravenously.
Keywords: solutol, colchicine, pharmacokinetics, formulation ingredients
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