A new method for kinetic studies of drug interactions in experimental animals during steady state. Controlled-rate application of valproic acid, phenobarbital and their combinations via implanted osmotic minipumps in the mouse.
Human therapeutic levels of valproic acid (VPA) and phenobarbital (PB) could be maintained in the mouse for a period of one week by controlled rate application (CRA) via subcutaneously implanted osmotic minipumps. PB-levels dropped markedly during one week of application, possibly by autoinduction. The interaction of PB and VPA was investigated by CRA of a mixture of both drugs. PB-levels were increased by VPA, probably due to enzyme inhibition, while VPA-levels were decreased by PB, probably by enzyme induction. Our results indicate tha CRA of drugs such as VPA and PB via implantable osmotic minipumps may be a valuable procedure for drug interaction studies during steady-state conditions.
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004343:Drug Implants; D004347:Drug Interactions; D005260:Female; D007700:Kinetics; D051379:Mice; D010634:Phenobarbital / Q000008:administration & dosage / Q000097:blood*; D014635:Valproic Acid / Q000008:administration & dosage / Q000097:blood*
D004343:Drug Implants; D014635:Valproic Acid; D010634:Phenobarbital