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.
Abramson
F P
FP
Department of Pharmacology, George Washington University Medical Center, Washington, DC.
D000284:Administration, Oral; D000818:Animals; D000983:Antipyrine / Q000493:pharmacokinetics*; D001682:Biological Availability; D004285:Dogs; D007275:Injections, Intravenous; D008297:Male; D010634:Phenobarbital / Q000493:pharmacokinetics / Q000494:pharmacology*
D000983:Antipyrine; D010634:Phenobarbital