Reversible metabolism and pharmacokinetics: application to prednisone-prednisolone

The simplest three pharmacokinetic models which apply in cases of reversible metabolism are described. Area under the curve (AUC) relationships are described which allow one to make a choice of which one of the three models may apply in a particular case. Expressions for clearances and other pharmacokinetic parameters are given. It is shown that biexponential time courses are expected after bolus intravenous administration although distribution is not involved in the models. In some cases dose/AUC or infusion rate/steady-state concentration yield simple clearances, while in other cases they are complex. AUC data obtained following oral administration of 5 mg doses of prednisone and prednisolone to 16 normal volunteers were analyzed with the new concepts and one of the models was found to apply. This new interpretation of such data results in some significant changes from application of classical pharmacokinetics.