A New Pharmacokinetic Approach for a Better Understanding of the Relationship Between the Terminal Half-Life of Drug and Its Physiologically Based Pharmacokinetic Parameters.

The terminal half-life (T) of a biphasic declining plasma concentration-time profile of a drug after intravenous administration is proportional to a ratio between its systemic clearance (CL) and volume of distribution at pseudo-distribution equilibrium (Vd). Due to lack of understanding of Vd simply known as a proportionality constant between the amount of drug in the body and its plasma concentration during the terminal phase, the effects of various physiologically based pharmacokinetic parameters of drug on T could not have been evaluated. The objective of the current study is to offer a new theoretical ground, using the Taylor series expansion, for a better understanding of relationships among T, CL, distributional clearance (CL) and volumes of distribution in the tissue compartment (V) and at steady state (Vd) of drug in a 2-compartment model after intravenous administration. Similar CL and Vd yet different T of drugs found in pharmacokinetic studies might be due to differences in CL and V of those drugs. In conclusion, the new equation (T ≈ 0.693 (Vd/CL + V/CL) explicitly shows how the physiologically based pharmacokinetic parameters of drug could affect its T after intravenous administration.