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J Pharm Sci. 2009 Oct;98(10):3850-61. doi: 10.1002/jps.21682.

Pharmacokinetic allometric scaling of antibodies: application to the first-in-human dose estimation.

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1
Office of Blood Review & Research, Center for Biologic Evaluation and Research, Food & Drug Administration, Maryland, USA. iftekhar.mahmood@fda.hhs.gov

Abstract

The objectives of this study are: (i) to evaluate the predictive performance of interspecies scaling for antibodies to predict clearance, volume of distribution at steady state, and half-life in humans from animal data and (ii) to estimate first-in-human dose based on the predicted human clearance. Four 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, (3) the product of clearance and brain weight versus body weight, and (4) the application of a fixed exponent of 0.75. Based on the predicted human clearance, six methods were used to estimate the first-in-human dose. The predicted pharmacokinetic parameters and the estimated first-in-human dose of antibodies were compared with the observed human values. The results of the study indicated that the clearance of antibodies can be predicted with reasonable accuracy in humans and a good estimate of first human dose can be obtained from the predicted human clearance.

PMID:
19177515
DOI:
10.1002/jps.21682
[Indexed for MEDLINE]
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