Pharmacokinetics, disposition, and plasma concentrations of dimethyl sulfoxide (DMSO) in the horse following topical, oral, and intravenous administration.

Abstract

Compartmental models were used to investigate the pharmacokinetics of intravenous (i.v.), oral (p.o.), and topical (TOP) administration of dimethyl sulfoxide (DMSO). The plasma concentration-time curve following a 15-min i.v. infusion of DMSO was described by a two-compartment model. Median and range of alpha (t1/2α ) and beta (t1/2β ) half-lives were 0.029 (0.026-0.093) and 14.1 (6.6-16.4) hr, respectively. Plasma concentration-time curves of DMSO following p.o. and TOP administration were best described by one-compartment absorption and elimination models. Following the p.o. administration, median absorption (t1/2ab ) and elimination (t1/2e ) half-lives were 0.15 (0.01-0.77) and 15.5 (8.5-25.2) hr, respectively. The plasma concentrations of DMSO were 47.4-129.9μg/ml, occurring between 15min and 4hr. The fractional absorption (F) during a 24-hr period was 47.4 (22.7-98.1)%. Following TOP administrations, the median t1/2ab and t1/2e were 1.2 (0.49-2.3) and 4.5 (2.1-11.0) hr, respectively. Plasma concentrations were 1.2-8.2μg/ml occurring at 2-4hr. Fractional absorption following TOP administration was 0.48 (0.315-4.4)% of the dose administered. Clearance (Cl) of DMSO following the i.v. administration was 3.2 (2.2-6.7)mlhr-1 kg-1 . The corrected clearances (ClF ) for p.o. and TOP administrations were 2.9 (1.1-5.5) and 4.5 (0.52-18.2)mlhr-1 kg-1 .