The effect of induction with phenobarbital on the kinetics and bioavailability of antipyrine in the dog.

In dogs, the chronic administration of 400 mg/d of phenobarbital produced peak plasma concentrations of 78 micrograms/ml which so markedly induced the metabolism of antipyrine that the conventional schemes by which antipyrine kinetics assess induction were rendered invalid. The bioavailability of antipyrine was only 20% due to first-pass metabolism. Induction raised the observed antipyrine clearance to 31 ml/min/kg, a value approaching hepatic blood flow. If one assumes antipyrine was an ideal test compound, one would calculate that metabolism was induced by a factor of 3.8. Acknowledging that antipyrine is nonideal, one can calculate a correct induction factor of 13.6. Oral, rather than intravenous, antipyrine is the metabolism test of choice under these conditions.