Protein binding and hepatic clearance: Discrimination between models of hepatic clearance with diazepam, a drug of high intrinsic clearance, in the isolated perfused rat liver preparation
- 1 April 1984
- journal article
- research article
- Published by Springer Nature in Journal of Pharmacokinetics and Biopharmaceutics
- Vol. 12 (2) , 129-147
- https://doi.org/10.1007/bf01059274
Abstract
The influence of protein binding on the extraction ratio, and availability, of diazepam has been examined in the single-pass isolated perfused rat liver preparation. Binding of diazepam was varied by adjusting the concentration of albumin in the perfusate. In the absence of binding the extraction ratio of diazepam was high, 0.93–0.995. Extraction decreased dramatically as the degree of binding was increased. The data are more consistent with the “parallel-tube” model than with the “well-stirred” model, two perfusion models that have been used to describe hepatic drug elimination.Keywords
This publication has 36 references indexed in Scilit:
- Protein binding and hepatic clearance: Studies with tolbutamide, a drug of low intrinsic clearance, in the isolated perfused rat liver preparationJournal of Pharmacokinetics and Biopharmaceutics, 1983
- Influence of plasma protein binding kinetics on hepatic clearance assessed from a “tube” model and a “well-stirred” modelJournal of Pharmacokinetics and Biopharmaceutics, 1981
- Effect of serum protein binding on pharmacokinetics and anticoagulant activity of phenprocoumon in ratsJournal of Pharmacokinetics and Biopharmaceutics, 1980
- Hepatic elimination of flowing substrates: The distributed modelJournal of Theoretical Biology, 1978
- Estimating the Dimension of a ModelThe Annals of Statistics, 1978
- Comparative Pharmacokinetics of Coumarin Anticoagulants XXX: Relationship between Total Clearance and Serum Protein Binding of Dicumarol in RatsJournal of Pharmaceutical Sciences, 1977
- Hepatic clearance of drugs. II. Experimental evidence for acceptance of the “well-stirred” model over the “parallel tube” model using lidocaine in the perfused rat liverin situ preparationJournal of Pharmacokinetics and Biopharmaceutics, 1977
- Hepatic clearance of drugs. I. Theoretical considerations of a “well-stirred” model and a “parallel tube” model. Influence of hepatic blood flow, plasma and blood cell binding, and the hepatocellular enzymatic activity on hepatic drug clearanceJournal of Pharmacokinetics and Biopharmaceutics, 1977
- Perfusion-limited effects of plasma drug binding on hepatic drug extractionLife Sciences, 1976
- Clearance concepts in pharmacokineticsJournal of Pharmacokinetics and Biopharmaceutics, 1973