Abstract
This tutorial examines the relationship between CL, F, and hepatic blood flow (QH) quantitatively at oral and i.v. administration as an answer to the quiz set for KSCPT members. In case of oral dosing, when hepatic blood flow increases, the hepatic clearance (CL) and bioavailability (F) increases in high-extraction ratio drugs according to the well-stirred model equations for hepatic clearance: CLH = QH·ER = QH∙fu∙CLint/(QH+fu∙CLint) and F = 1 − ER Despite such a clear relationship, many students may feel it rather paradoxical that the increased CL (thus decreasing the AUC) causes increased F and thus the AUC (F∙Dose/CLH) remains unchanged. This tutorial clarifies that the degree to which CL increase fails to match that of the QH increase, and thus the decreased ER (= CL/QH) that results in the increased F. Contemplating this simple, but seemingly paradoxical phenomenon may help students gain a deeper understanding of the first-pass effect.
REFERENCES
1.Rowland M., Tozer TN. Clinical pharmacokinetics and pharmacodynamics: concepts and applications. 4th ed.Lippincott Williams & Wilkins;Baltimore: 2011. p. 125–126.
2.Rowland M., Tozer TN. Clinical pharmacokinetics and pharmacodynamics: concepts and applications. 4th ed.Lippincott Williams & Wilkins;Baltimore: 2011. 196.