Prediction of the disposition of propafenone in humans and dogs from pharmacokinetic parameters in other animal species.
Most allometric studies performed until now have considered results obtained by different authors. The parameters mentioned in these studies reflect experiments made under very different conditions and have been calculated by assembling these heterogeneous data reported in the literature. In this paper, we present an allometric study of propafenone carried out in eight animal species, all treated and handled under the same conditions, and taking into account their weight to calculate different pharmacokinetic parameters. Propafenone plasma concentration-time data were analyzed by a model-independent method, and the pharmacokinetic parameters (Y) were correlated with body weight (B) using linear regression analysis by the equation Y = aBx. In addition, human and dog pharmacokinetic parameters were predicted from the results obtained in the other seven species and compared with the experimentally observed values. We demonstrated that these predictions are subject to great error when drugs with extensive metabolism, such as propafenone, are considered.
Puigdemont
A
A
Department of Pharmacology, School of Veterinary, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Guitart
R
R
de Mora
F
F
Arboix
M
M
D000328:Adult; D000818:Animals; D001835:Body Weight; D002417:Cattle; D003627:Data Interpretation, Statistical; D004285:Dogs; D005260:Female; D006736:Horses; D006801:Humans; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008954:Models, Biological; D011405:Propafenone / Q000493:pharmacokinetics*; D011817:Rabbits; D012044:Regression Analysis; D012756:Sheep
D011405:Propafenone