Pharmacokinetics of diclofenac and its interaction with sulfonamide-trimetoprim in sheep

Diclofenac and sulfonamide-trimethoprim combination are two compounds used together in the treatment of infectious diseases and metabolized in the liver by the P450 enzyme. Sulfonamide-trimethoprim inhibits these enzymes. This changes the pharmacokinetics of drugs used in combination with sulfonamide-trimethoprim. Eighteen animals, 6 sheep in each group, were used in the study. 1. Group intramuscularly 1 mg/kg dose diclofenac, 2. Group intravenose 1 mg/kg dose and diclofenac (1 mg/kg) in the third group were administred intramusculary and a sulfadoxine-trimethoprim (5 mg/kg) mixture was administered intravenose. Blood was taken at 2, 5, 10, 15, 30, 45 minutes and at 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 and 24 hours after the administration of the drugs. Their serum was extracted in the laboratory,extracted and applied to High Pressur Liquid Chromatography (HPLC). The plasma concentration-time data following i.v. administration of diclofenac t½ 1,481±0,056 h, AUC0-t 3,407± 0,127µg/ml/h, AUC0-∞ 3,549± 0,143 µg/ml/h, AUMC 5,096± 0,343 µg/ml/h, Vz 0,603±0,015 L/kg, MRT 1,428± 0,039 h, Cl 0,284±0,011 L/kg/h respectively. Following İM administration of diclofenac alone and in conjunction with sulfadoxin-trimetoprim, the t½ 2,313±0,016- 3,628±0,099 h, tmax 0,750±0,000-1,000±0,000 h, AUC0-t 3,313±0,063- 3,524±0,055 µg/ml/h, AUC0-∞ 3,467±0,065- 4,065±0,078 µg/ml/h, AUMC 12,219±0,236- 22,689±2,377 µg/ml/h, Vz 0,964± 0,020-1,452±0,171 L/kg, MRT 3,523±0,020-5,543±0,465 h, Cl 0,288±0,005-0,246±0,004 L/kg/h, bioavailability İM application it was found to be 93 % and 99 % in kombined application. Co-administration of sulfadoxin-trimetoprim resulted in increases in tmax, t½, AUC0-t, AUC0-∞, AUMC, Vz, MRT, Cl MRT and bioavailability. This may be due to direct inhibition of cytochrome P450 enzymes sulfadoxine-trimethoprim. In this case, we think that it would be appropriate to read just the döşe of diclofenac in sheep.