Pharmacokinetics of Diclofenac in Sheep Following Intravenous and Intramuscular Administration

Diclofenac is an important nonsteroidal anti-inflammatory drug that is commonly used in both humans and animals. The aim of this work was to examine the pharmacokinetics of diclofenac in sheep after intravenous and intramuscular dosing. Diclofenac (1 mg/kg) was administered to ten clinically healthy-male Najdi sheep intravenously or intramuscularly (n = 5 each). Blood samples (5 ml) were collected and serum was separated for drug analysis by high performance liquid chromatography with UV detection. Diclofenac pharmacokinetic parameters were determined by non-compartmental analysis. Diclofenac is quickly eliminated from sheep with a terminal Tm of 2-3 hr for both routes of administration. Total diclofenac clearance after intravenous and intramuscular administration was 87.86±10.78 and 85.69±18.23 ml/hr/kg, respectively. Apparently, the absolute bioavailability of IM diclofenac is excellent (-100%), which indicates that a similar dose could be given IM instead of IV if needed. Given this data, diclofenac should be administered 2-3 times daily in sheep (via these routes) to maintain therapeutic concentrations. Additional studies are needed to evaluate the route of elimination of diclofenac in sheep including metabolites formation and the significance of enterohepatic circulation in this process.