Xenobiotica; the fate of foreign compounds in biological systems
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Review Comparative Study
Interspecies scaling and comparisons in drug development and toxicokinetics.
1. Methods of interspecies extrapolation using physiological models and allometric scaling have been reviewed with their possible application to drug development, both for candidate drug selection and the interpretation of toxicokinetic data. 2. Physiological models offer a mechanistic approach to extrapolation from one species to another, examining individual components which interrelate to produce the characteristics of the whole system. ⋯ For routine drug development, however, allometric scaling is potentially more useful since it uses data which are routinely obtained and the calculations are relatively simple. 6. The problems of intraspecies scaling from high-dose data to low-dose predictions are discussed with respect to current models of dose levels. A new approach is proposed using a modified Hill equation based on drug exposure, which should allow for a more meaningful determination of the toxicity of a compound with different drug exposures.(ABSTRACT TRUNCATED AT 400 WORDS)