Application of Organ Clearance to Estimation of the In Vivo Hepatic Extraction Ratio.
Organ clearance, which has been derived from the organ blood flow and extraction ratio (E), has been extensively used by clinical pharmacologists to explain the pharmacokinetics of many drugs in health and disease. For example, the extent of hepatic clearance or E (Eh) of drugs would determine their response to changes in the liver blood flow and/or activities of the metabolizing enzymes. Although Eh may be obtained directly by cannulating internal blood vessels, the method is invasive. Therefore, indirect methods have been used to estimate Eh from the peripheral blood concentration-time data after intravascular administration of drugs. Additionally, these indirect methods require an estimate of the liver blood flow in the patients or animals. However, some investigators use plasma concentrations and/or liver plasma flow for the estimation of Eh, which could potentially result in significant errors. It is shown here that when plasma concentrations are used along with liver blood flow, an overestimation or underestimation of the true value will result if the blood: plasma concentration (B:P) ratio is >1 or < 1, respectively, with the estimated Eh being different from the true value by a factor equal to the B:P ratio. On the other hand, the use of plasma concentrations and plasma liver flow will always result in an overestimation of the true Eh unless the drug does not penetrate the red blood cells. It is concluded that for the accurate estimation of Eh from the in vivo data, the blood concentration and blood flow should be used.
Department of Biomedical and Pharmaceutical Sciences, School of Pharmacy, Chapman University Rinker Health Science Campus, 9401 Jeronimo Road, Irvine, CA 92618, USA. mehvar@chapman.edu.
Reza
R
Mehvar
D000818:Animals; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*
D004364:Pharmaceutical Preparations