Pharmacokinetics and effects of repeated administration of phenylbutazone in neonatal calves

Susan Diane Semrad From the Department of Medical Sciences, University of Wisconsin, Madison, WI 53706 (Semrad, McClure) and the Analytical Toxicology Laboratory, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210 (Sams, Kaminski).

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J Trenton McClure From the Department of Medical Sciences, University of Wisconsin, Madison, WI 53706 (Semrad, McClure) and the Analytical Toxicology Laboratory, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210 (Sams, Kaminski).

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Richard Alvin Sams From the Department of Medical Sciences, University of Wisconsin, Madison, WI 53706 (Semrad, McClure) and the Analytical Toxicology Laboratory, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210 (Sams, Kaminski).

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Lucille Marie Kaminski From the Department of Medical Sciences, University of Wisconsin, Madison, WI 53706 (Semrad, McClure) and the Analytical Toxicology Laboratory, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210 (Sams, Kaminski).

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Summary

Age, species, and disease state may substantially alter the disposition and clearance of pharmacologic agents. This is particularly important when drugs with low therapeutic index are used in ill neonates. Pharmacokinetic variables for phenylbutazone were determined in 24- to 32-hour-old healthy and endotoxemic calves after iv administration of a single dose (5 mg/kg of body weight, iv). Elimination halflife was 207 and 168 hours, and clearance was 0.708 and 0.828 ml/kg/h in healthy and endotoxemic calves, respectively. Intravenous infusion of endotoxin at the dose (2 μg/kg over 4 hours) given did not significantly alter any of the calculated pharmacokinetic variables. Serum thromboxane B2 concentration was significantly (P = 0.05) suppressed for 3 hours after phenylbutazone administration in healthy calves and for 4 hours in endotoxin-challenged calves. Daily administration of phenylbutazone (10 mg/kg loading, then 5 mg/kg for 9 days) to healthy and endotoxemic calves failed to induce any lesions consistent with nonsteroidal anti-inflammatory drug toxicosis.

Summary

Age, species, and disease state may substantially alter the disposition and clearance of pharmacologic agents. This is particularly important when drugs with low therapeutic index are used in ill neonates. Pharmacokinetic variables for phenylbutazone were determined in 24- to 32-hour-old healthy and endotoxemic calves after iv administration of a single dose (5 mg/kg of body weight, iv). Elimination halflife was 207 and 168 hours, and clearance was 0.708 and 0.828 ml/kg/h in healthy and endotoxemic calves, respectively. Intravenous infusion of endotoxin at the dose (2 μg/kg over 4 hours) given did not significantly alter any of the calculated pharmacokinetic variables. Serum thromboxane B2 concentration was significantly (P = 0.05) suppressed for 3 hours after phenylbutazone administration in healthy calves and for 4 hours in endotoxin-challenged calves. Daily administration of phenylbutazone (10 mg/kg loading, then 5 mg/kg for 9 days) to healthy and endotoxemic calves failed to induce any lesions consistent with nonsteroidal anti-inflammatory drug toxicosis.

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