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 (AUC0→∞) 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

Toxicity of diclofenac sodium salt in Yucatan minipigs (Sus scrofa) following 4 weeks of daily intramuscular administration

“…In toxicokinetics results, the systemic exposure (AUC last ) of the DSS administration intramuscularly on Day1 is about 380 times higher than dermal administration based on 10 mg/kg/day [ 14 ]. The AUC last following intramuscular administration at a dose 2.5 mg/kg/day similar to that of a low dose receiving 2 mg/kg in this study [ 25 , 26 ].…”

Pharmacokinetics and residues elimination of diclofenac sodium administration in pigs by a new HPLC/MS method

“…DF usage was limited in veterinary medicine, and there was a little data on the pharmacokinetics of DF in target animal species. In veterinary practice, DF was indicated and suitable for treatment of various inflammatory, degenerative post-trauma disorders and lameness in horses, cattle and pigs, as well as pre-operative treatment for cataract extraction (6,7). Among them, the pharmacokinetics and metabolism have been studied through major ways of oral and intravenous administration.…”

Effects of Intramuscular Diclofenac Use on Lipid Peroxidation and Skeletal Muscle Histology in Balb-C Mice

“…Diclofenac sodium interferes with the action of cyclooxygenase (COX), which is an enzyme that converts arachidonic acid into prostaglandins, thromboxanes and prostacyclins 2,3 . Thus diclofenac inhibits prostaglandin biosynthesis, also reduces leukotriene formation, both of which contribute to its anti-inflammatory activity 4 . The inhibitory action of diclofenac sodium is the main mechanism responsible for both the efficiency and the adverse side effects of diclofenac.…”