A New Pharmacokinetic Approach for a Better Understanding of the Relationship Between the Terminal Half-Life of Drug and Its Physiologically Based Pharmacokinetic Parameters
Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:109 |
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| Enthalten in: |
Journal of pharmaceutical sciences - 109(2020), 3 vom: 15. März, Seite 1421-1423 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kwon, Younggil [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 17.06.2021 Date Revised 17.06.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.xphs.2019.12.010 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM304642053 |
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| 520 | |a Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
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