PHARMACOKINETICS AND EFFECTS OF REPEATED ADMINISTRATION OF PHENYLBUTAZONE IN NEONATAL CALVES

Age, species, and disease state may substantially alter the dispositio n and clearance of pharmacologic agents. This is particularly importan t when drugs with low therapeutic index are used in ill neonates. Phar macokinetic variables for phenylbutazone were determined in 24- to 32- hour-old healthy and endotoxemic calves after IV administration of a s ingle dose (5 mg/kg of body weight, IV). Elimination half-life was 207 and 168 hours, and clearance was 0.708 and 0.828 ml/kg/h in healthy a nd endotoxemic calves, respectively. Intravenous infusion of endotoxin at the dose (2 mu g/kg over 4 hours) given did not significantly alte r any of the calculated pharmacokinetic variables. Serum thromboxane B -2 concentration was significantly (P = 0.05) suppressed for 3 hours a fter phenylbutazone administration in healthy calves and for 4 hours i n 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.