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Interspecies Scaling: Role of Protein Binding in the Prediction of Clearance from Animals to Humans
Author(s) -
Mahmood Iftekhar
Publication year - 2000
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/009127000004001214
Subject(s) - clearance , clearance rate , body weight , allometry , metabolic clearance rate , chemistry , plasma clearance , pharmacokinetics , pharmacology , biology , endocrinology , medicine , urology , ecology
The objective of this study is to evaluate whether unbound clearance of a drug can be predicted more accurately than total clearance using the allometric approach and if there is any real advantage of predicting unbound clearance over total clearance. The total and unbound clearance of 20 randomly selected drugs were scaled up from the animal data (at least three animal species) obtained from the literature. Three methods were used to generate plots to scale up the clearance values: (1) total or unbound clearance versus body weight (simple allometric equation), (2) the product of total or unbound clearance and maximum life span potential (MLP) versus body weight, and (3) the product of total or unbound clearance and brain weight versus body weight. The results of this study indicate that there will be instances when unbound clearance can be predicted better than total clearance or vice versa. In conclusion, unbound clearance cannot be predicted any better than total clearance.