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J Pharm Sci. 2004 Jan;93(1):177-85.

Interspecies scaling of protein drugs: prediction of clearance from animals to humans.

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Division of Clinical Trial Design and Analysis, Office of Therapeutic Research and Review, Food & Drug Administration, Woodmont Office Center I, Suite 200N, 1401 Rockville Pike, Rockville, Maryland 20852, USA. Mahmoodi@CBER.FDA.GOV


The objective of this study was to evaluate the interspecies scaling for therapeutic protein drugs to predict the systemic clearance in humans from animal data. This study was undertaken to examine whether the rule of exponents of Mahmood and Balian for the prediction of clearance of nonprotein drugs can also be extended to macromolecules. Three different methods were used to predict clearance in humans: (1). clearance versus body weight (simple allometry), (2). the product of clearance and maximum life-span potential (MLP) versus body weight, and (3). the product of clearance and brain weight versus body weight. Data from 15 therapeutic proteins were analyzed, and the results indicated that the clearance of protein drugs can be predicted accurately using simple allometry or brain weight depending on the exponents of the simple allometry. Furthermore, these 15 drugs were scaled up using two species and the predicted clearance was compared with the predicted clearance obtained from more than two species. It was found that more than two species are needed for a reliable prediction of clearance.

[Indexed for MEDLINE]

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