Pharmacokinetics of phenylbutazone and oxyphenabutazone in the pig

Abstract

The kinetics of phenylbutazone (pbz) and its main metabolite oxyphenbutazone (oxpbz) were investigated in seven pigs in order to determine if this animal might serve as a model for human investigations. The study was performed in two stages, one as single dose experiments using intravenous injection, the second as infusion experiments. The rate of elimination for both compounds was demonstrated to be much faster than in man. Similar results have been observed in several other animal species. The degree of protein binding (pbz 98%, ox-pbz 97%), the apparent specific volume of distribution (pbz 0.18 1/kg, ox-pbz 0.28 1/kg) and the renal clearance were found to be similar to results obtained in man and rat. Ox-pbz had a higher renal clearance (0.13 ml/min/kg) than pbz (0.003 ml/min/kg) but still the renal excretion constituted only a small fraction of the total elimination (pbz 0.5%, ox-pbz 5%). Provided real steady state conditions were obtained during the infusion experiments calculations based on the results from the single dose experiments in the same animal revealed that between 20 and 60% of the injected pbz was metabolized to the ring-hydroxylation product (ox-pbz). It is concluded that the pig model is not superior to other animal models for studies of pbz/ox-pbz. The rapid elimination pattern is the main problem in relation to human investigations.