Dose-response behavior of the induction of alpha 1-acid glycoprotein by phenobarbital in the dog.
Three-week dosing periods at one of six oral phenobarbital doses between 15 and 400 mg/day were used to achieve steady states for induction of plasma alpha 1-acid glycoprotein concentration (AGP) in beagle dogs. In this way, the characteristics of the dose-response relationship between phenobarbital concentration and the extent of induction could be evaluated. With the 400 mg/day dose of phenobarbital, AGP increased nearly 13-fold. The response of AGP was found to depend on the square of the phenobarbital concentration. Analysis of the decay of AGP when phenobarbital dosing was discontinued showed a kinetic pattern governed by multiple rate processes. This was the result of persistence of the phenobarbital, the turnover of some metabolic precursor to AGP, and the turnover of AGP itself.
D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D008433:Mathematics; D008954:Models, Biological; D009961:Orosomucoid / Q000097:blood*; D010634:Phenobarbital / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics
D009961:Orosomucoid; D010634:Phenobarbital