Pharmacokinetics of ketoprofen in healthy foals less than twenty-four hours old

Jeff R. Wilcke From the Departments of and Large Animal Clinical Sciences (Crisman, Scarratt) and Biomedical Sciences and Pathobiology (Wilcke), Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, and Departments of Veterinary Medicine Administration and Veterinary Clinical Sciences (Sams), College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

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Mark V. Crisman From the Departments of and Large Animal Clinical Sciences (Crisman, Scarratt) and Biomedical Sciences and Pathobiology (Wilcke), Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, and Departments of Veterinary Medicine Administration and Veterinary Clinical Sciences (Sams), College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

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W. Kent Scarratt From the Departments of and Large Animal Clinical Sciences (Crisman, Scarratt) and Biomedical Sciences and Pathobiology (Wilcke), Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, and Departments of Veterinary Medicine Administration and Veterinary Clinical Sciences (Sams), College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

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Richard A. Sams From the Departments of and Large Animal Clinical Sciences (Crisman, Scarratt) and Biomedical Sciences and Pathobiology (Wilcke), Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, and Departments of Veterinary Medicine Administration and Veterinary Clinical Sciences (Sams), College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

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Abstract

Objective

To determine pharmacokinetic variables that describe disposition of ketoprofen after its IV administration to foals < 24 hours old.

Animals

6 healthy foals (1 male and 5 females); mean age, 12.5 (range, 8.5 to 17) hours at time of dose administration.

Procedure

Ketoprofen was administered IV to foals at a dosage of 2.2 mg/kg of body weight. Ketoprofen concentration in plasma samples was analyzed, using high-performance liquid chromatography. Concentration versus time profiles were analyzed according to standard pharmacokinetic techniques. Blood samples were obtained from foals by jugular venipuncture at defined times during a 48-hour period. Samples were centrifuged, and plasma was frozen at −70 C until analyzed. One-, two-, and three-compartment analyses were conducted. The most appropriate model was determined by use of Akaike's information criterion analysis.

Results

Plasma concentration versus time profiles were best described, using a two-compartment open model. Clearance (normalized for body weight) was significantly lower than that determined for adult horses. Volume of distribution (normalized for body weight) was larger than that determined for adult horses. Mean (harmonic) plasma half-life for healthy foals < 24 hours old was 4.3 hours.

Clinical Relevance

Although additional factors, such as dehydration or sepsis, must be considered on a case-by-case basis, the dose of ketoprofen administered to foals < 24 hours old should be different from the dose administered to adult horses. Under similar clinical circumstances, doses in foals should be increased by as much as 1.5 times to produce comparable therapeutic concentrations; longer dose intervals, based on clinical response, would be necessary to avoid drug toxicity. (Am J Vet Res 1998;59:290–292)

Abstract

Objective

To determine pharmacokinetic variables that describe disposition of ketoprofen after its IV administration to foals < 24 hours old.

Animals

6 healthy foals (1 male and 5 females); mean age, 12.5 (range, 8.5 to 17) hours at time of dose administration.

Procedure

Ketoprofen was administered IV to foals at a dosage of 2.2 mg/kg of body weight. Ketoprofen concentration in plasma samples was analyzed, using high-performance liquid chromatography. Concentration versus time profiles were analyzed according to standard pharmacokinetic techniques. Blood samples were obtained from foals by jugular venipuncture at defined times during a 48-hour period. Samples were centrifuged, and plasma was frozen at −70 C until analyzed. One-, two-, and three-compartment analyses were conducted. The most appropriate model was determined by use of Akaike's information criterion analysis.

Results

Plasma concentration versus time profiles were best described, using a two-compartment open model. Clearance (normalized for body weight) was significantly lower than that determined for adult horses. Volume of distribution (normalized for body weight) was larger than that determined for adult horses. Mean (harmonic) plasma half-life for healthy foals < 24 hours old was 4.3 hours.

Clinical Relevance

Although additional factors, such as dehydration or sepsis, must be considered on a case-by-case basis, the dose of ketoprofen administered to foals < 24 hours old should be different from the dose administered to adult horses. Under similar clinical circumstances, doses in foals should be increased by as much as 1.5 times to produce comparable therapeutic concentrations; longer dose intervals, based on clinical response, would be necessary to avoid drug toxicity. (Am J Vet Res 1998;59:290–292)

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