Novel approach to bioavailability testing: statistical method for comparing drug input calculated by a least-squares...

A novel approach to bioavailability testing is presented. The approach is model independent because it does not assume a specific pharmacokinetic model and does not use absorption, distribution, or elimination rate constants or a volume term. The method, which requires intravenous administration, is compared to classical bioavailability evaluation methods. Evaluation of drug input is based on the same assumptions required for using the area under the curve. No extrapolation beyond the last data point is required. Two statistics are derived that enable a comparison of the rate and the cumulative amount of input of two inputs for various times. A differential confidence profile is calculated that allows a more detailed and intrinsic bioavailability comparison than previous methods. The approach is demonstrated on simulated data containing random noise and shows satisfactory performance.