Pharmacokinetics of diclofenac in pigs after intramuscular administration of a single dose

Abstract

The pharmacokinetics of diclofenac was studied in 10 clinically normal male Yorkshire pigs, following intramuscular (i.m.) administration of a single dose of diclofenac-sodium (2.5 mg/kg body weight). Diclofenac serum concentrations were determined by high-pressure-liquid-chromatography (HPLC), with UV detection (226 nm). Following i.m. administration all individual diclofenac serum levels best fitted the one-compartment open model for extravascular administration. The maximal diclofenac serum concentration of 5.88 ± 0.934 mg/L was reached after 0.80 ± 0.35 h. The absorption half-life was 0.36 ± 0.25 h, and the area under the concentration vs. time curve (AUC 0→∞ ) was 20.32 ± 4.521 mgh/L. A monoexponential concentration decline and small volume of distribution (Vd) of 0.29 ± 0.100 L/kg indicated a rapid, but not extensive distribution of diclofenac between central and peripheral compartment(s). Total clearance was 0.13 ± 0.034 L/h/kg, and elimination half-life was short (1.67 ± 0.743 h), as a result of a rapid distribution and extensive metabolism of diclofenac in the pig's body. When administered i.m. to pigs, diclofenac is absorbed and distributed rapidly. Distribution is not extensive, suggesting that diclofenac is predominantly retained in the central compartment. The elimination of the drug from the pig's circulation is also rapid, most of it probably being a result of extensive metabolism in the liver.