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On the Origin of the Apparent Volume of Distribution and Its Significance in Pharmacokinetics 被引量:3

On the Origin of the Apparent Volume of Distribution and Its Significance in Pharmacokinetics
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摘要 The apparent volume of distribution was defined for the first time as the phase volume that can hold the total amount of a substance at the measured phase substance concentration, in a system composed of two immiscible media that are in contact under conditions of constant phase volumes, at equilibrium. Its value is not affected by the total system solute mass and it only depends on the total system volume, the phase volumes and the affinity of the solute for the two phases in the system. Using this new concept of the apparent volume of distribution, we were able to demonstrate that under certain conditions compartment volumes in multi-compartment and multi-phasic pharmacokinetic models represent the actual physiological volumes of body fluids accessible by drugs. The classical pharmacokinetic models are now fully explained and can be used to provide accurate estimation of the pharmacokinetic parameters for hydrophilic drugs. In contrast, in the absence of tissue-plasma partition coefficients, lipophilic drugs that do not follow a one-compartment model are unlikely to be adequately described with classical multi-compartment pharmacokinetic models. The apparent volume of distribution was defined for the first time as the phase volume that can hold the total amount of a substance at the measured phase substance concentration, in a system composed of two immiscible media that are in contact under conditions of constant phase volumes, at equilibrium. Its value is not affected by the total system solute mass and it only depends on the total system volume, the phase volumes and the affinity of the solute for the two phases in the system. Using this new concept of the apparent volume of distribution, we were able to demonstrate that under certain conditions compartment volumes in multi-compartment and multi-phasic pharmacokinetic models represent the actual physiological volumes of body fluids accessible by drugs. The classical pharmacokinetic models are now fully explained and can be used to provide accurate estimation of the pharmacokinetic parameters for hydrophilic drugs. In contrast, in the absence of tissue-plasma partition coefficients, lipophilic drugs that do not follow a one-compartment model are unlikely to be adequately described with classical multi-compartment pharmacokinetic models.
作者 Michalakis Savva Michalakis Savva(South University, Savannah, USA)
机构地区 South University
出处 《Journal of Biosciences and Medicines》 2022年第1期78-98,共21页 生物科学与医学(英文)
关键词 Apparent Volume of Distribution Partition Coefficient Phase Extraction Pharmacokinetic Compartmental Modeling Physiologically-Based Pharmacokinetic Modeling Apparent Volume of Distribution Partition Coefficient Phase Extraction Pharmacokinetic Compartmental Modeling Physiologically-Based Pharmacokinetic Modeling
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