Pharmacokinetics of ibuprofen after intravenous and oral administration and assessment of safety of administration to healthy foals

Objective-To determine pharmacokinetics of ibuprofen in healthy foals and t o determine clinical effects after oral administration for 6 days. Animals-7 healthy 5- to 10-week-old foals. Procedure-Serum concentrations of ibuprofen were measured after IV and oral (nasogastric tube) administration at dosages of 10 and 25 mg/kg of body we ight. Foals were given ibuprofen (25 mg/kg, PO,q 8 h) as a paste for 6 days . Serum and urine were obtained before and after the 6-day period. Results-Half-life of elimination (K-el t1/2) of IV-administered ibuprofen t ie, 10 and 25 mg/kg,was 79 and 108 minutes, maximal serum concentration (C- MAX)was 82 and 160 mu g/ml, and clearance was 0.003 and 0.002 L/kg/min, res pectively. At the higher dosage, clearance was significantly fewer and C-MA X was significantly higher. Ibuprofen given via nasogastric tube resulted i n K-el t1/2 of 81 and 100 minutes and C-MAX of 22 and 52 mu g/ml for 10 and 25 mg/kg, respectively. The absorption half-life was 13 minutes, and bioav ailability ranged from 71 to 100%. Foals remained healthy during oral admin istration of ibuprofen. Serum urea nitrogen, creatinine, and L-iditol dehyd rogenase values increased significantly, and gamma-glutamyltransferase (GGT ) activity and osmolality decreased, but all measurements remained within r eference ranges. Urine GGT activity doubled; Necropsy did not reveal gross or histologic renal lesions attributable to ibuprofen. Acute gastric ulcers were evident in 1 feat, although clinical signs of ulcers were not observe d. Conclusions and Clinical Relevance-lbuprofen can be given safely to healthy foals at dosages less than or equal to 25 mg/kg every 8 hours for up to 6 days.