The pharmacokinetics of diclofenac and its interaction with sulfadoxine-trimethoprim in sheep

• Published in: Small ruminant research Vol. 221; p. 106950
• Main Authors: Alkaç, Zeliha Keskin, Yerlikaya, Şevda Maçin, Korkak, Fatih Ahmet, Tanyıldızı, Sadettin, Hark, Betül Dağoğlu, Dağoğlu, Gürdal
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.04.2023
• Subjects: Diclofenac; Pharmacokinetics; Sheep; Sulfadoxine; Trimethoprim; Trimethoprim; Sheep; Sulfadoxine; Pharmacokinetics; Diclofenac
• ISSN: 0921-4488; 1879-0941
• DOI: 10.1016/j.smallrumres.2023.106950

In this study, the pharmacokinetics of diclofenac was determined following a single intravenous and intramuscular administration of diclofenac alone and co-administration with sulfadoxine-trimethoprim in sheep. A randomized, controlled, experimental study. A total of 18 healthy male Ivesi sheep were used in the study (2–4 years old, with an average weight of 50 ± 5 kg). Diclofenac was administered alone in the 1st group intramuscular (1 mg/kg), intravenous (1 mg/kg) in the 2nd group, and together (intramuscular diclofenac (1 mg/kg) and intravenous sulfadoxine -trimethoprim (5 mg/kg)) in the 3rd group. Blood was collected at 2, 5, 10, 15, 30, and 45 min and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 h following the administration. The plasma concentration of diclofenac was determined with high-performance liquid chromatography (HPLC). Pharmacokinetic parameters were analyzed using a non-compartmental analysis pharmacokinetic model. The elimination half-life (t½), area under the plasma concentration-time curve (AUC), mean residence time (MRT), volume of distribution at steady-state (Vd), total body clearance (ClT), and bioavailability (F) values following the diclofenac were evaluated IM alone 2.31 ± 0.01 h, 3.31 ± 0.06 h* µg/mL, 3.52 ± 0.02 h, 0.96 ± 0.02 L/kg, 0.28 ± 0.00 mL/h/kg, 93%, respectively. When co-administered with sulfadoxine-trimethoprim the same kinetic values of diclofenac were 3.62 ± 0.09 h, 3.52 ± 0.05 h* µg/mL, 5.54 ± 0.46 h, 1.45 ± 0.17 L/kg, 0.24 ± 0.00 mL/h/kg and 99%, respectively. Sulfadoxine-trimethoprim increased the t½, AUC, MRT, Vd, and F values of diclofenac at statistically significant levels, and decreased the ClT value. The results of the study indicate that the pharmacokinetics of diclofenac are altered when used with sulfadoxine-trimethoprim. Therefore, if the two drugs are used together, a new dose adjustment should be made for diclofenac. •Antibacterial and nonsteroidal anti-inflammatory drugs (NSAID) co-administration is prevalent in sheep.•It was determined that the pharmacokinetics of diclofenac changed when used together with sulfadoxine-trimethoprim.•Therefore, a new dose adjustment of diclofenac should be made when co-administered with sulfadoxine-trimethoprim.