Non-compartmental analysis of pharmacokinetic data after multiple intravenous and oral administration

Non-compartmental analysis is routinely used to determine the pharmacokinetic parameters such as area under the curve (AUC), area under the first moment curve (AUMC), clearance (CL), mean residence time (MRT), terminal half life (t1/2) and volume of distribution (Vd). These parameters are important to define the fate of a drug after administration by a particular route. It is well known that the AUC after a single dose is equivalent to that after multiple dose at steady state during one dosing interval. However, this relationship is not true for AUMC. Hence, it is not possible to calculate MRT as the ratio of AUMC and AUC from multiple dose data. It was the purpose of this presentation to evaluate the calculation of MRT for single and multiple dosing after intravenous and oral administration and compare two different approaches to determine MRT from multiple dose data. The results show that after multiple dosing MRT is most reliably determined by continuous sampling after the end of the last dosing interval until no more drug can be detected.