title: Visualization of plasma and tissue binding using dose fractions parameter.
abstract: A novel concept of dose fractions, based on the distribution of total bioavailable dose between the six combinations of location and binding state in Øie-Tozer's model is suggested as a way to visualize the distribution pharmacokinetics of a drug. The concept of dose fractions provides a sharper terminology in discussions of drug distribution allowing for a more precise description of the state and location of a drug within a system. In medicinal chemistry literature, the free fraction of a drug in plasma is a commonly discussed factor affecting the exposure to free drug while tissue binding is less well addressed. The free dose fraction, defined as the fraction of the bioavailable dose existing in free form, is suggested as a potentially valuable term for such discussions. Presently, drugs with high (>95%) plasma protein binding are viewed with skepticism, the rational behind which is questioned. The plasma protein bound dose fraction defined as the fraction of the total available dose, which is bound to plasma proteins, is suggested as a measure of the risk for problems related to fluctuations in free drug exposure due to variations in the concentration of drug binding plasma protein.
authors.affiliation: Department of Pharmaceutical Biosciences, Division of Pharmaceutical Bioinformatics, Biomedical Centre, Uppsala University, Uppsala, SE 751 24, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Svennebring
mesh_terms: D001682:Biological Availability; D001798:Blood Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D010599:Pharmacokinetics
chemical_list: D001798:Blood Proteins; D002352:Carrier Proteins
keywords: disposition; distribution; dose fraction; in vitro/in vivo correlations; protein binding