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Interspecies scaling: predicting oral clearance in humans
1Division of Pharmaceutical Evaluation 1 (HFD-860), Office of Clinical Pharmacology and Biopharmaceutics, Food & Drug Administration, Rockville, MD 20852, USA. Mahmoodi@CDER.FDA.GOV
American Journal of Therapeutics
|January 10, 2002
Summary
This study evaluated interspecies scaling methods to predict oral drug clearance in humans using animal data. Allometric equations, particularly those relating clearance to body weight, proved most effective for accurate predictions.
Area of Science:
- Pharmacokinetics
- Drug Metabolism and Transport
- Comparative Physiology
Background:
- Predicting human drug clearance from animal data is crucial for drug development.
- Existing allometric scaling methods for systemic clearance require evaluation for oral clearance prediction.
Purpose of the Study:
- To test the interspecies scaling approach for predicting human oral clearance using animal data.
- To evaluate the applicability of Mahmood and Balian's rule of exponents for oral clearance prediction.
Main Methods:
- Utilized three log-log plot methods for scaling clearance values: simple allometry (clearance vs. body weight), clearance*MLP vs. body weight, and clearance*brain weight vs. body weight.
- Analyzed data from 32 diverse drugs to compare prediction accuracy.
Main Results:
- Allometric equations demonstrated effectiveness in scaling clearance values across species.
- The study identified specific allometric approaches that best predict oral clearance in humans.
Conclusions:
- Interspecies scaling using allometric equations is a viable method for predicting human oral drug clearance.
- Clearance prediction accuracy can be optimized by selecting appropriate allometric models based on drug properties and physiological parameters.