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

Younggil Kwon

Journal of pharmaceutical sciences 2020 Mar

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The terminal half-life (T1/2) 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 (Vdβ). Due to lack of understanding of Vdβ, 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 T1/2 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 T1/2, CL, distributional clearance (CLd) and volumes of distribution in the tissue compartment (VT) and at steady state (Vdss) of drug in a 2-compartment model after intravenous administration. Similar CL and Vdss yet different T1/2 of drugs found in pharmacokinetic studies might be due to differences in CLd and VT of those drugs. In conclusion, the new equation (T1/2 ≈ 0.693 (Vdss/CL + VT/CLd) explicitly shows how the physiologically based pharmacokinetic parameters of drug could affect its T1/2 after intravenous administration. Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Citation

Younggil Kwon. A New Pharmacokinetic Approach for a Better Understanding of the Relationship Between the Terminal Half-Life of Drug and Its Physiologically Based Pharmacokinetic Parameters. Journal of pharmaceutical sciences. 2020 Mar;109(3):1421-1423