Prediction of absolute bioavailability of medicines in adults and children from oral clearance

Abstract

Aim: Two empirical methods were used to predict the absolute bioavailability (F) of medicines in adults and children following oral administration in the absence of intravenous (IV) dosing. This study systematically evaluates the predictive performance of Equation 1 to predict F in adults and children.

Methods: Equation 3 [F = Q/(Q + CL_oral)] was used for the prediction of F in adults and children. In Equation 3, clearance is the observed oral clearance following oral administration of a medicine and Q is either liver blood or plasma flow rate. The predictive performance of Equation 3 was evaluated in adults and children for three categories of medicines; medicines which are mainly metabolized in the liver, medicines which are metabolized both in the liver and the gut, and medicines which are mainly renally excreted. From the literature, oral clearance and F values for adults and children were obtained. The predictive performance of these two methods (blood or plasma flow rate) was assessed by comparing the predicted F of the medicines used in this study with the observed F (obtained from clinical studies).

Results: More than 90% predicted F values were within 0.5–2-fold prediction error in adults and children by both methods for all three categories of medicines. Plasma flow rate provided slightly better results than the blood flow rate.

Conclusions: The proposed methods indicate that the estimation of F of medicines in adults and children is possible with reasonable accuracy (within 0.5–2-fold prediction error). The method is useful to estimate F, especially in children, because it is not ethical to administer medicines by both IV and oral routes to children just for the sake of estimating F.

Keywords

absolute bioavailability / allometry / children / oral clearance / liver blood flow / plasma flow rate

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