The estimation of hepatic clearance, Cl h , using in vitro data on metabolic stability of compound, its protein binding and blood-plasma equilibrium concentration ratio is commonly performed using well-stirred, parallel tube or dispersion models. It appears that for ionizable drugs there is a differ
Consistency of the novel equations for determination of hepatic clearance and drug time course in liver that account for the difference in drug ionization in extracellular and intracellular tissue water
β Scribed by Leonid M. Berezhkovskiy; Ning Liu; Jason S. Halladay
- Publisher
- John Wiley and Sons
- Year
- 2012
- Tongue
- English
- Weight
- 58 KB
- Volume
- 101
- Category
- Article
- ISSN
- 0022-3549
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β¦ Synopsis
Intrinsic clearances of seven diverse compounds in rat liver microsomes were measured at intracellular pH 7.0 and extracellular pH 7.4. The obtained values were quite close for each compound. These results confirm the validity of the recently published novel equations for calculation of hepatic clearance and drug time course in liver that account for pH differences in extracellular water and hepatocytes.
π SIMILAR VOLUMES
A consistent account of the assumptions of the well-stirred perfusion limited model leads to the equation for the organ tissue that does not coincide with that often presented in books and papers. The difference in pharmacokinetic profiles calculated by the valid and the commonly used equations coul