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

Babetta A. Breuhaus From the Departments of Food Animal and Equine Medicine (Breuhaus, DeGraves, Honore), and Anatomy, Physiological Sciences and Radiology (Papich), College of Veterinary Medicine North Carolina State University, Raleigh, NC 27606.

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Fred J. DeGraves From the Departments of Food Animal and Equine Medicine (Breuhaus, DeGraves, Honore), and Anatomy, Physiological Sciences and Radiology (Papich), College of Veterinary Medicine North Carolina State University, Raleigh, NC 27606.

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Erika K. Honore From the Departments of Food Animal and Equine Medicine (Breuhaus, DeGraves, Honore), and Anatomy, Physiological Sciences and Radiology (Papich), College of Veterinary Medicine North Carolina State University, Raleigh, NC 27606.

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Mark G. Papich From the Departments of Food Animal and Equine Medicine (Breuhaus, DeGraves, Honore), and Anatomy, Physiological Sciences and Radiology (Papich), College of Veterinary Medicine North Carolina State University, Raleigh, NC 27606.

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Abstract

Objective

To determine pharmacokinetics of ibuprofen in healthy foals and to 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 weight. 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 (Kel t1/2) of IV-administered ibuprofen (ie, 10 and 25 mg/kg), was 79 and 108 minutes, maximal serum concentration (Cmax) was 82 and 160 μg/ml, and clearance was 0.003 and 0.002 L/kg/min, respectively. At the higher dosage, clearance was significantly lower and Cmax was significantly higher. Ibuprofen given via nasogastric tube resulted in Kel t1/2 of 81 and 100 minutes and Cmax of 22 and 52 μg/ml for 10 and 25 mg/kg, respectively. The absorption half-life was 13 minutes, and bioavailability ranged from 71 to 100%. Foals remained healthy during oral administration of ibuprofen. Serum urea nitrogen, creatinine, and l-iditol dehydrogenase values increased significantly, and γ-glutamyltransferase (GGT) activity and osmolality decreased, but all measurements remained within reference ranges. Urine GGT activity doubled. Necropsy did not reveal gross or histologic renal lesions attributable to ibuprofen. Acute gastric ulcers were evident in 1 foal, although clinical signs of ulcers were not observed.

Conclusions and Clinical Relevance

Ibuprofen can be given safely to healthy foals at dosages ≤ 25 mg/kg every 8 hours for up to 6 days. (Am J Vet Res 1999;60:1066-1073)

Abstract

Objective

To determine pharmacokinetics of ibuprofen in healthy foals and to 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 weight. 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 (Kel t1/2) of IV-administered ibuprofen (ie, 10 and 25 mg/kg), was 79 and 108 minutes, maximal serum concentration (Cmax) was 82 and 160 μg/ml, and clearance was 0.003 and 0.002 L/kg/min, respectively. At the higher dosage, clearance was significantly lower and Cmax was significantly higher. Ibuprofen given via nasogastric tube resulted in Kel t1/2 of 81 and 100 minutes and Cmax of 22 and 52 μg/ml for 10 and 25 mg/kg, respectively. The absorption half-life was 13 minutes, and bioavailability ranged from 71 to 100%. Foals remained healthy during oral administration of ibuprofen. Serum urea nitrogen, creatinine, and l-iditol dehydrogenase values increased significantly, and γ-glutamyltransferase (GGT) activity and osmolality decreased, but all measurements remained within reference ranges. Urine GGT activity doubled. Necropsy did not reveal gross or histologic renal lesions attributable to ibuprofen. Acute gastric ulcers were evident in 1 foal, although clinical signs of ulcers were not observed.

Conclusions and Clinical Relevance

Ibuprofen can be given safely to healthy foals at dosages ≤ 25 mg/kg every 8 hours for up to 6 days. (Am J Vet Res 1999;60:1066-1073)

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