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• W2065078412 abstract "Binding of drugs to plasma proteins is commonly considered in pharmacokinetics as being in an instantaneous equilibrium. Although if the timescale of dissociation of drug–protein complex becomes comparable to the time that a drug molecule spends in blood while passing through the elimination organ, the kinetics of protein binding may influence the organ clearance. This appears possible for the compounds that have large dissociation energy from protein. Typically, the dissociation of drug–protein complex is fast. However, the longest experimentally observed average bound time of drug to human albumin was as much as 11 min, whereas the time that a drug molecule spends in blood while passing through the liver is around 19 s. The equations for the calculation of hepatic clearance (Clh) with the account of protein binding kinetics are derived for the well‐stirred and parallel‐tube models. It turns out that for drugs with very low extraction ratio, the influence of protein binding kinetics on Clh is negligible; however, for drugs with high extraction ratio, it may lead to substantially smaller values (possibly by an order of magnitude) of Clh compared with that provided by the common calculations." @default.
• W2065078412 created "2016-06-24" @default.
• W2065078412 creator A5087131657 @default.
• W2065078412 date "2012-10-01" @default.
• W2065078412 modified "2023-09-24" @default.
• W2065078412 title "Determination of Hepatic Clearance with the Account of Drug–Protein Binding Kinetics" @default.
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• W2065078412 doi "https://doi.org/10.1002/jps.23235" @default.
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