An extended physiological pharmacokinetic model of methadone disposition in the rat: validation and sensitivity analysis.
An extended physiological model of methadone disposition in the rat was constructed and evaluated in various tests of model validity. A separate circulation model of the fetus was included due to the large tissue concentration differences obtained after a constant rate infusion but also to propose the use of this type of model for optimization of toxicological tests. Simulations were performed with the animal model and scaled-up models of humans to elucidate the determinants of methadone disposition. The rationale of the use of an extended model for methadone was also discussed.
Department of Pharmacokinetics and Biopharmaceutics, Uppsala University, Sweden.
J L
JL
Gabrielsson
T
T
Groth
D000818:Animals; D005260:Female; D008691:Methadone / Q000493:pharmacokinetics*; D008954:Models, Biological; D011247:Pregnancy; D051381:Rats
D008691:Methadone