PHARMACOKINETIC INTERACTIONS BETWEEN REPEATED DOSE PHENYLBUTAZONE ANDGENTAMICIN IN THE HORSE

This study examined the pharmacokinetics of steady-state phenylbutazon e and single bolus intravenous gentamicin when administered together i n the horse. The trial design was completed as a cross-over with seven thoroughbred horses. In the first phase each horse received 2.2 mg/kg gentamicin intravenously. After a 2-week washout, each horse received 4.4 mg/kg phenylbutazone intravenously every 24 h for 5 days. On the fourth day each horse received gentamicin as before. Plasma was harves ted for gentamicin concentration determination by fluorescence polariz ation by high-performance liquid chromatography. All gentamicin data w ere best approximated by a two-compartment open model using sequential , weighted non-linear regression. Pharmacokinetic parameters were calc ulated using model-dependent formulae. Phenylbutazone data were analys ed by non-compartmental methods. Phenylbutazone induced a 49% increase in the rate of gentamicin return to the central compartment form peri pheral tissues (k(21)) (P < 0.05) and there was a trend to a 24% incre ase in k(12) (P = 0.052). The gentamicin elimination half-life was dec reased 23% and the V-d(area) was reduced by 26%. No induction by genta micin of changes in pheznylbutazone pharmacokinetics were detected. In summary, phenylbutazone induced changes to the rate and extent of dis tribution and elimination of gentamicin. Therefore, care should be exe rcised in the use of aminoglycosides in equine patients concurrently m aintained on phenylbutazone.