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ANALYSIS OF NONLINEAR PHARMACOKINETIC SYSTEMS AND THE NONLINEAR DISPOSITION OF PHENYLBUTAZONE IN EQUINE (HORSES)

Abstract

Phenylbutazone was administered to six thoroughbred horses in a cross-over design in which the horses received co-administration of ranitidine or control treatment. The study started with single-dose oral administrations of 2.2, 4.4, and 8.8 mg/kg phenylbutazone, and then multiple-dose administrations of twice daily dose of 2.2, 4.4, and 8.8 mg/kg phenylbutazone with a 1-week washout period between trials. Blood samples were collected at various times up to 24 hr. after singledose and up to 72 hr. after multiple-dose phenylbutazone administration. Pharmacokinetic analyses were performed for phenylbutazone, and its major metabolites oxyphenbutazone and γ-hydroxyphenylbutazone. Twelve-hr single-dose and 72-hr multiple-dose plasma concentration profiles of phenylbutazone with concomitant ranitidine treatment were not significantly different from the control. The

Material Code

PBM_EGzwb

Reference

REFERENCE Browne, T. R., G. K. Szabo, C. McEntegart, J. E. Evans, B. A. Evans, J. J. Miceli, C. Quon, C. L. Dougherty, J. Kres and H. Davoudi (1993). "Bioavailability studies of drugs with nonlinear pharmacokinetics: II. Absolute bioavailability of intravenous phenytoin prodrug at therapeutic phenytoin serum concentrations determined by double-stable isotope technique." J Clin Pharmacol 33(1): 89-94. Browne, T. R., G. K. Szabo, G. E. Schumacher, D. J. Greenblatt, J. E. Evans and B. A. Evans (1992). "Bioavailability studies of drugs with nonlinear pharmacokinetics: I. Tracer dose AUC varies directly with serum concentration." J Clin Pharmacol 32(12): 1141-1145.

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