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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/14215

Title: A Meta-Analytical Framework to Include Historical Data in Allometric Scaling
Authors: Bijnens, Luc
Van Den Bergh, An
Sinha, Vikash
Geys, Helena
Molenberghs, Geert
Verbeke, Tobias
Kasim, Adetayo
Straetemans, Roel
De Ridder, Filip
Balmain-Mackie, Claire
Issue Date: 2012
Abstract: To predict human pharmacokinetics such as the clearance and the plasma concentration profile of a new compound, many animal-based methods have been used in the past. They are typically based on animal information on the compound of interest. This translational step is crucial in pharmaceutical development since it is used to estimate the human pharmacokinetic (PK) parameters and the starting dose for the first-in-human study. Among the currently used methods, allometric scaling is probably one of the oldest and simplest, because it uses essentially body weight and brain weight to correct for species in the prediction of the human PK measures. The assumption that body weight can be used as a surrogate for an animal species is key in the current methods. It also assumes that there is a general biological process that holds in mammal species such as mice, rats, rabbits, monkeys, dogs, and man. Brain weight, lifespan, and a number of other corrections are often successfully used to fine-tune the relationship between clearance and body weight. This research project investigates the variability that goes along with current practice and suggests a meta-analytical approach to control for the variability of human unbound clearance. The new approach also establishes a model linking the animal data to human data using historical data in a way that has not been done before.
Notes: [Bijnens, Luc] Hasselt Univ, Ctr Stat CenStat, B-2340 Beerse, Belgium. [Bijnens, Luc; Van Den Bergh, An; Sinha, Vikash; Geys, Helena; De Ridder, Filip; Balmain-Mackie, Claire] Janssen Pharmaceut NV, Johnson & Johnson Pharmaceut R&D, B-2340 Beerse, Belgium. [Molenberghs, Geert] Katholieke Univ Leuven, I BioStat, B-3590 Diepenbeek, Belgium. [Verbeke, Tobias] OpenAnalyt BVBA, B-2220 Heist Op Den Berg, Belgium. [Kasim, Adetayo] Hasselt Univ, I BioStat, B-3590 Diepenbeek, Belgium. [Straetemans, Roel] Ablynx NV, B-9052 Ghent, Belgium. lbijnens@its.jnj.com; avdberg2@its.jnj.com; vshinha@its.jnj.com; hgeys@its.jnj.com; geert.molenberghs@uhasselt.be; tverbek1@its.jnj.com; adetayo.kasim@uhasselt.be; roel.straetemans@ablynx.com; fdridder@its.jnj.com; cmackie@its.jnj.com
URI: http://hdl.handle.net/1942/14215
DOI: 10.1080/19466315.2012.707493
ISI #: 000308132100011
ISSN: 1946-6315
Category: A1
Type: Journal Contribution
Validation: ecoom, 2013
Appears in Collections: Research publications

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