Interspecies allometric scaling: prediction of clearance in large animal species: Part II: mathematical considerations

Abstract

Interspecies scaling is a useful tool for the prediction of pharmacokinetic parameters from animals to humans, and it is often used for estimating a first-time in human dose. However, it is important to appreciate the mathematical underpinnings of this scaling procedure when using it to predict pharmacokinetic parameter values across animal species. When cautiously applied, allometry can be a tool for estimating clearance in veterinary species for the purpose of dosage selection. It is particularly valuable during the selection of dosages in large zoo animal species, such as elephants, large cats and camels, for which pharmacokinetic data are scant. In Part I, allometric predictions of clearance in large animal species were found to pose substantially greater risks of inaccuracies when compared with that observed for humans. In this report, we examine the factors influencing the accuracy of our clearance estimates from the perspective of the relationship between prediction error and such variables as the distribution of body weight values used in the regression analysis, the influence of a particular observation on the clearance estimate, and the 'goodness of fit' (R(2)) of the regression line. Ultimately, these considerations are used to generate recommendations regarding the data to be included in the allometric prediction of clearance in large animal species.

Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 670 Drug Compounds

“…Previous reports have focused on prediction methods that utilize animal pharmacokinetic data (Caldwell et al, 2004;Ward and Smith, 2004a,b;Jolivette and Ward, 2005;Evans et al, 2006;Mahmood et al, 2006;Martinez et al, 2006;Tang and Mayersohn, 2006;Fagerholm, 2007;McGinnity et al, 2007) and in vitro data (Obach et al, 1997;Lombardo et al, 2002Lombardo et al, , 2004Nestorov et al, 2002;Riley et al, 2005;Grime and Riley, 2006). Recently, the availability of computational chemistry methodologies has increased, and these have been applied to the prediction of human pharmacokinetics and/or general absorption-distribution-metabolism-excretion-toxicology properties (Cruciani et al, 2005;Ghafourian et al, 2006;Gleeson et al, 2006;Lombardo et al, 2006;Gleeson, 2007;Gunturi and Narayanan, 2007;Norinder and Bergstroem, 2007).…”

Animal models of BMAA neurotoxicity: A critical review

“…It is a well established fact that effective and/or toxic doses of different substances, on mg/kg body weight bases, vary widely between animal species, and simple repetition of the effective dose from one animal species to another can result in a lack of effect or severe toxicity (Calabrese et al, 1992;Boxenbaum and DiLea, 1995;Mahmood et al, 2006;Martinez et al, 2006). The primary reason for this phenomenon is the differences in the size of animals which affects the body weight to surface area ratio.…”

“…Thus size must be taken into account in interspecies scaling of drugs and toxins (Calabrese et al, 1992;Boxenbaum and DiLea, 1995;Mahmood, 2005;Mahmood et al, 2006;Martinez et al, 2006). This approach, which is used for first-in-human dose selection based on pharmacokinetic data from small animals (mice, rat, rabbit, guinea pig, monkey, dog), is also used in veterinary medicine, particularly in the treatment of large zoo animal species (Boxenbaum and DiLea, 1995;Mahmood et al, 2006;Martinez et al, 2006). Depending on the method of scaling, e.g.…”

Aplicabilidade da extrapolação alométrica em protocolos terapêuticos para animais selvagens

“…Apesar do uso em algumas espécies de animais selvagens, os métodos de extrapolação alométrica ainda não foram bem validados e alguns artigos farmacocinéticos ilustram falhas específicas (JACOBSON, 1996;MARTÍN-JIMÉNES & RIVIERE, 2001; ou o contraindicam para agentes com ampla biotransformação hepática (JACOBSON, 1996;MAHMOOD et al, 2006;MARTINEZ et al, 2006). Dentre um grupo de 44 fármacos, somente 11 demonstraram ser bons candidatos para extrapolação interespécies de parâmetros farmacocinéticos (meia-vida) em espécies de relevância em Medicina Veterinária, a saber: tetraciclina, oxitetraciclina, clortetraciclina, eritromicina, cefapirina, ampicilina, gentamicina, apramicina, cabenicilina, diazepam e prednisolona.…”