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

Mark V. Crisman From the Departments of Large Animal Clinical Sciences (Crisman) 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, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210 (Sams).

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 DVM, MS
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Jeff R. Wilcke From the Departments of Large Animal Clinical Sciences (Crisman) 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, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210 (Sams).

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Richard A. Sams From the Departments of Large Animal Clinical Sciences (Crisman) 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, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210 (Sams).

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 PhD

Abstract

Objective

To determine pharmacokinetic variables that describe the disposition of flunixin after IV administration of flunixin meglumine to foals < 24 hours old.

Animals

6 healthy foals, 2 males and 4 females (mean age, 11.6 hours; range, 6 to 22.5 hours).

Procedure

Flunixin (as flunixin meglumine) was administered to foals at a dosage of 1.1 mg/kg of body weight. Flunixin concentration in plasma samples was analyzed, using gas chromatography/mass spectroscopy. Concentration versus time profiles were analyzed according to standard pharmacokinetic techniques. Blood samples were obtained from foals by jugular venipuncture at defined intervals over 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 Akaike's information criterion analysis.

Results

Plasma concentration versus time profiles were best described, using a two-compartment open model. Clearance was significantly lower than that determined for older foals and adult horses. Volume of distribution was larger than that determined for adults. Mean plasma halflife for healthy foals < 24 hours old was 8.5 hours.

Conclusions and Clinical Relevance

Although additional factors (eg, dehydration or sepsis) must be considered on a case-by-case basis, flunixin meglumine should be administered differently to foals < 24 hours old, compared with adults. Under similar clinical circumstances, doses in foals should be increased by as much as 1.5 times to induce comparable therapeutic concentrations; longer dose intervals, on the basis of clinical response, would be necessary to avoid drug toxicity. (Am J Vet Res 1996;57:1759–1761)

Abstract

Objective

To determine pharmacokinetic variables that describe the disposition of flunixin after IV administration of flunixin meglumine to foals < 24 hours old.

Animals

6 healthy foals, 2 males and 4 females (mean age, 11.6 hours; range, 6 to 22.5 hours).

Procedure

Flunixin (as flunixin meglumine) was administered to foals at a dosage of 1.1 mg/kg of body weight. Flunixin concentration in plasma samples was analyzed, using gas chromatography/mass spectroscopy. Concentration versus time profiles were analyzed according to standard pharmacokinetic techniques. Blood samples were obtained from foals by jugular venipuncture at defined intervals over 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 Akaike's information criterion analysis.

Results

Plasma concentration versus time profiles were best described, using a two-compartment open model. Clearance was significantly lower than that determined for older foals and adult horses. Volume of distribution was larger than that determined for adults. Mean plasma halflife for healthy foals < 24 hours old was 8.5 hours.

Conclusions and Clinical Relevance

Although additional factors (eg, dehydration or sepsis) must be considered on a case-by-case basis, flunixin meglumine should be administered differently to foals < 24 hours old, compared with adults. Under similar clinical circumstances, doses in foals should be increased by as much as 1.5 times to induce comparable therapeutic concentrations; longer dose intervals, on the basis of clinical response, would be necessary to avoid drug toxicity. (Am J Vet Res 1996;57:1759–1761)

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