The pharmacokinetics of phenylbutazone and its interaction with dexamethasone in chicks

Abstract

The present study aims to investigate the influence of dexamethasone administration on the pharmacokinetics of phenylbutazone and its plasma concentration as well as its pharmacological interaction in a chick model. The analgesic median effective doses (ED50s) of phenylbutazone and dexamethasone are separately evaluated as 5.60 and 0.63 mg/kg, IP, and their ED50s are estimated and reduced to 1.76 and 0.19 mg/kg, IP, respectively. The type of pharmacological interaction between phenylbutazone and dexamethasone is synergistic as determined by the isobolographic analysis. The phenylbutazone administration at 11.20 mg/kg, IP has plasma concentrations of 39.83, 66.17, 48.00, 35.30, 26.50 and 13.33 µg/ml in the estimated times of 0.25, 0.5, 1, 2, 4, and 24 hours, respectively. These concentrations are increased to 57.00, 384.17, 210.67, 138.67, 65.50 and 50.10 µg/ml as dexamethasone 1.26 mg/kg, IP is given by 43, 426, 339, 293, 147 and 276%. Phenylbutazone pharmacokinetics are increased and result in an elevation in an area under the curve (AUC0-∞) 196%, area under the moment curve (AUMC0-∞) 140%, elimination rate constant (Kel) 50%, and maximum concentration (Cmax) 426%. However, other parameters are reduced to include half-life (t1/2β) 33%, mean residence time (MRT) 18%, steady state of the volume of distribution (Vss) 78%, and clearance (Cl) 60%. The overall findings reveal a synergism as a type of pharmacological interaction between phenylbutazone and dexamethasone. In addition, a change in phenylbutazone pharmacokinetics and its plasma concentration which improves phenylbutazone therapeutic efficiency in the chick model is noticed.