The average fold error for human CL predictions for N=176 drugs was 2.25 with 79% of the drugs having a fold error less than 3. Human in-vivo PK predictions can be obtained using the simple allometric scaling relationships CL Human ≈ 40 CL Rat (L/hr), V ss Human ≈ 200 V ss Rat (L), and t 1/2 Human ≈ 4 t 1/2 Rat (hr). We have shown, using a large diverse set of drugs, that a fixed exponent allometric scaling approach can be used to predict human in-vivo PK parameters CL, V ss and t 1/2 solely from rat in-vivo PK data with acceptable accuracy for making go/no-go decisions in drug discovery. We have investigated the accuracy of the in-vivo correlation between rat and human for the prediction of the total systemic clearance (CL), the volume of distribution at steady state (V ss), and the half-life (t 1/2) using simple allometric scaling techniques. In a drug discovery environment, reasonable go/no-go human in-vivo pharmacokinetic (PK) decisions must be made in a timely manner with a minimum amount of animal in-vivo or in-vitro data.
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