Towards a Better Prediction of Peak Concentration, Volume of Distribution and Half-Life after Oral Drug Administration in Man, Using Allometry

Background: It is imperative that new drugs demonstrate adequate pharmacokinetic properties, allowing an optimal safety margin and convenient dosing regimens in clinical practice, which then lead to better patient compliance. Such pharmacokinetic properties include suitable peak (maximum) plasma drug concentration (Cmax), area under the plasma concentration-time curve (AUC) and a suitable half-life (t1/2). The Cmax and t1/2 following oral drug administration are functions of the oral clearance (CL/F) and apparent volume of distribution during the terminal phase by the oral route (Vz/F), each of which may be predicted and combined to estimate Cmax and t1/2. Allometric scaling is a widely used methodology in the pharmaceutical industry to predict human pharmacokinetic parameters such as clearance and volume of distribution. In our previous published work, we have evaluated the use of allometry for prediction of CL/F and AUC. In this paper we describe the evaluation of different allometric scaling approaches for the prediction of Cmax, Vz/F and t 1/2 after oral drug administration in man.