[Interspecies allometric scaling in pharmacokinetics of drugs].
Allometric scaling is an empirical examination of the relationships between the pharmacokinetic parameters and size (usually body weight, ratio of organ- and body weight, breathing number, etc.). Interspecies pharmacokinetics tend to approximate, the organism, as the sum of organs and tissues according to material balance. The allometric equations for the pharmacokinetic parameters were applied to scale the data with respect to pharmacokinetic time and remove the chronological time dependency. When the data of at least three species are available, the pharmacokinetic parameters can be fit according to body weight in log-log regression. Allometric scaling is not applicable in all cases, only when the selected species has similar physiological behaviour, such as protein-binding, metabolism, etc. Valuable information for the evaluation of the effect and the biopharmaceutical characteristics may emerge from more creative data analysis based on all result collected during the preclinical evaluation of a new drug. Author examined the applicability of the interspecies scaling method in the case of a new drug depogen, using drotaverin as reference. The pharmacokinetic data were collected from mouse, rat and dog and during the evaluation human data were applied too. The usual pharmacokinetic parameters were determined (MRT, MAT, beta, etc.), the results of allometric analysis were collected and the standard deviation of measured and calculated values were given.
Sylvia
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Semmelweis Orvostudományi Egyetem, Gyógyszerészeti Intézet, Budapest.
D000818:Animals; D001835:Body Weight; D002415:Cats; D004285:Dogs; D004338:Drug Combinations; D006801:Humans; D051379:Mice; D009929:Organ Size; D010208:Papaverine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010276:Parasympatholytics / Q000493:pharmacokinetics*; D051381:Rats; D012044:Regression Analysis; D013045:Species Specificity; D013806:Theophylline / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014018:Tissue Distribution