Free Drug Theory

Talevi, Alan; Bellera, Carolina L.

doi:10.1007/978-3-030-51519-5_51-1

The ADME Encyclopedia 2021

DOI: 10.1007/978-3-030-51519-5_51-1

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Free Drug Theory

Alan Talevi

Carolina L. Bellera

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2022

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Cited by 1 publication

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Tissue Drug Concentration

Fagiolino

Vázquez

2022

CPD

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Blood flow enables the delivery of oxygen and nutrients to the different tissues of the human body. Drugs follow the same route as oxygen and nutrients; thus, drug concentrations in tissues are highly dependent on the blood flow fraction delivered to each of these tissues. Although the free drug concentration in blood is considered to correlate with pharmacodynamics, the pharmacodynamics of a drug is actually primarily commanded by the concentrations of drug in the aqueous spaces of bodily tissues. However, the concentrations of drug are not homogeneous throughout the tissues, and they rarely reflect the free drug concentration in the blood. This heterogeneity is due to differences in the blood flow fraction delivered to the tissues and also due to membrane transporters, efflux pumps, and metabolic enzymes. The rate of drug elimination from the body (systemic elimination) depends more on the driving force of drug elimination than on the free concentration of drug at the site from which the drug is being eliminated. In fact, the actual free drug concentration in the tissues results from the balance between the input and output rates. In the present paper, we develop a theoretical concept regarding solute partition between intravascular and extravascular spaces; discuss experimental research on aqueous/non-aqueous solute partitioning and clinical research on microdialysis; and present hypotheses to predict in-vivo elimination using parameters of in-vitro metabolism.

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Tissue Drug Concentration

Fagiolino

Vázquez

2022

CPD

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Free Drug Theory

Cited by 1 publication

References 14 publications

Tissue Drug Concentration

Tissue Drug Concentration

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