Scaling interspecies pharmacokinetic

Much has been published on the extrapolation of in vivo data from animals to humans. These include pharmacokinetic data (e.g. half-lives, plasma concentrations, clearances and rates of metabolism) and pharmacodynamic data (e.g. effective and toxic doses). Two excellent reviews present many examples and insightful discussions on isometric and allometric relationships, time scales, interspecies pharmacokinetic and pharmacodynamic scaling, and physiological models (Boxenbaum and D Souza, 1990 Chappell and Mordenti, 1991). 

H Boxenbaum, R Ronfeld. Interspecies pharmacokinetic scaling and the Dedrick plots. Am J Physiol 245 R768-R774, 1983. 

Boxenbaum, H. (1984) Interspecies pharmacokinetic scaling and the evolutionary-comparative paradigm. Drug Metabolism Reviews, 15, 1071-1121. 

Interspecies pharmacokinetic scaling, biological design and neoteny, 19, 139... 

Ritschel, W. A., Vachharajani, N. N., Johnson, R. D., and Hussain, A. S. (1992). The allo-metric approach for interspecies scaling of pharmacokinetic parameters. Comp. Biochem. Physiol. C 103 249-253. 

Hayakawa H, Fukushima Y, Kato H, et al. Metabolism and disposition of novel des-fluoro quinolone garenoxacin in experimental animals and an interspecies scaling of pharmacokinetic parameters. Drug Metab Dispos 2003 31 1409-1418. 

Jolling, K., Perez-Ruixo, J. J., Hemeryck, A., Vermeulen, A., Greway, T. Mixed-effects modelling of the interspecies pharmacokinetic scaling of pegylated human erythropoietin. Eur J Pharm Sci 2005, 24 465-475. 

Gamer RC, Barker J, Flavell C et al. (2000) A validation study comparing accelerator MS and liquid scintillation counting for analysis of 14C-labelled drugs in plasma, urine and faecal extracts. J Pharm Biomed Anal 24 197-209 Hayakawa H, Fukushima Y, Kato H et al. (2003) Metabolism and disposition of novel des-fluoro quinolone garenoxacin in experimental animals and an interspecies scaling of pharmacokinetic parameters. Drug Metab Dispos 31 1409-1418... 

Mahmood I, Balian JD. Interspecies scaling Predicting pharmacokinetic parameters of antiepileptic drugs in humans form animals with special emphasis on clearance. J Pharm Sci 1996 85 411-4. 

Interspecies pharmacokinetic scaling, biological design and neoteny. 19. 139 A Kinetic approach to the mechanism of drug action. 3. 57 Laboratory models of atherosclerosis. 9, 41... 

Boxenbaum, H. and D Souza, R.W. (1990) Interspecies pharmacokinetic scaling, biological design and neoteny, in Advances in Drug Research, Vol. 19 (ed. B. Testa), Academic Press Ltd, London, pp. 139-196. 

V. F. Cosson, E. Fuseau, C. Efthymiopoulos, and A. Bye, Mixed effect modeling of sumatriptan pharmacokinetics during drug development. I Interspecies allometric scaling. J Pharmacokinet Biopharm 25 149-167 (1997). 

Mahmood, I. Interspecies pharmacokinetic scaling Principles, applications, and limitations. In Pharmacokinetics in drug development Clinical study design and analysis. (Bonate, P.L., and Howard, D., Eds.). AAPS Press, Alexandria, VA, 2004, pp. 423-444. 

Lave, T. et al.. Interspecies pharmacokinetic comparisons and allometric scaling of napsagartran, a low molecnlar weight thrombin inhibitor, J. Pharm. Pharmacol., 51 85-91, 1999. 

Hall C, Lueshen E, Mo at A, Linninger AA. 2012. Interspecies scaling in pharmacokinetics a novel whole-body physiologically based modeling framework to discover drug biodistribution mechanisms in vivo. J Pharm Sci 101 1221-1241. 

Patel BA, Boudinot FD, Schinazi RF, Gallo JM, Chu CK (1990) Comparative pharmacokinetics and interspecies scaling of 3 -azido-3 -deoxythymidine (AZT) in several mammalian species. J Pharmacobiodyn 13 206-211... 

In order to extrapolate laboratory animal results to humans, an interspecies dose conversion must be performed. Animals such as rodents have different physical dimensions, rates of intake (ingestion or inhalation), and lifespans from humans, and therefore are expected to respond differently to a specified dose level of any chemical. Estimation of equivalent human doses is usually performed by scaling laboratory doses according to observable species differences. Unfortunately, detailed quantitative data on the comparative pharmacokinetics of animals and humans are nonexistent, so that scaling methods remain approximate. In carcinogenic risk extrapolation, it is commonly assumed that the rate of response for mammals is proportional to internal surface area... 

Lin, J.H., Applications and limitations of interspecies scaling and in vitro extrapolation in pharmacokinetics, Drug Metab. Dispos. 26(12), 1202-1212, 1998. 

Lave, T., Coassolo, P., Reigner, B., Prediction of hepatic metabolic clearance based on interspecies allometric scaling techniques and in vitro-in vivo correlations, Clin. Pharmacokinet. 1999, 36, 211-321 and references cited therein. 

Jezequel, S. G., Fluconazole interspecies scaling and allometric relationships of pharmacokinetic properties, J. Pharm. Pharmacol. 1994, 46, 196-199. 

Obach et al. [27] proposed a model to predict human bioavailability from a retrospective study of in vitro metabolism and in vivo animal pharmacokinetic (PK) data. While their model yielded acceptable predictions (within a factor of 2) for an expansive group of compounds, it relied extensively on in vivo animal PK data for interspecies scaling in order to estimate human PK parameters. Animal data are more time-consuming and costly to obtain than are permeability and metabolic clearance data hence, this approach may be limited to the later stages of discovery support when the numbers of compounds being evaluated are fewer. 

If physiologically based pharmacokinetic (PBPK) models cannot be used, interspecies extrapolation is best undertaken by means of scaling according to basal metabolic rate, see Section 5.3.2.3. A second aspect, interspecies variability, should be considered in cases where a higher than average level of safety (achieved by consideration of a higher percentile of the substances) is desired. 

Pharmacokinetics and metabolism - absorption, distribution, metabolism and excretion (ADME), including potential for interactions, polymorphisms of drug metabolising enzymes and exposures in man predicted from interspecies allometric scaling... 

Holleran, J.L. et al. (2005) Plasma pharmacokinetics, oral bioavailabihty, and interspecies scaling of the DNA melhyltransferase inhibitor, zebularine. Clinical Cancer Research, 11, 3862-3868. 

Boxenbaum, H. 1982. Interspecies scaling, allometry, physiological time, and the ground plan of pharmacokinetics. 

Apart from of being able to screen compounds more rapidly, another advantage of predicting human pharmacokinetic properties in silico, is that the models are generated with human data. In certain cases, such as prediction of metabolism, this may offer an advantage over scaling animal data, as it circumvents the problems of interspecies differences (Li, 2001). 

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