The kinetics of a drug eliminated by first-order processes in a perfusion-limited isolated perfused organ system are examined. In this model, the mean clearance, determined by dividing the dose by the area under the blood concentration profile, and the steady-state clearance are shown to be equal. The perfusion model and the compartmental model are compared and contrasted. Effects of blood flow and reservoir size on drug clearance are examined. Similarities and differences between the isolated and the in vivoorgan system are explored. The virtue of using clearance, instead of half-life, as a correlative parameter between these systems is stressed.
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Supported by Grant NIGMS 16496 from the National Institutes of Health, U.S. Public Health Service, Bethesda, Maryland.
This paper was submitted to a Consulting Editor who served as the Journal Editor during its review process.
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Rowland, M., Benet, L.Z. & Graham, G.G. Clearance concepts in pharmacokinetics. Journal of Pharmacokinetics and Biopharmaceutics 1, 123–136 (1973). https://doi.org/10.1007/BF01059626
- drug clearances
- perfusion models
- isolated perfused organ systems
- pharmacokinetic clearance
- steady-state clearance