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Visualization of Plasma and Tissue Binding Using Dose Fractions Parameter
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2014 (English)In: Drug development research (Print), ISSN 0272-4391, E-ISSN 1098-2299, Vol. 75, no 7, 425-437 p.Article in journal (Refereed) Published
Abstract [en]

A novel concept of dose fractions, based on the distribution of total bioavailable dose between the six combinations of location and binding state in Oie-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.

Place, publisher, year, edition, pages
2014. Vol. 75, no 7, 425-437 p.
Keyword [en]
disposition, distribution, dose fraction, in vitro, in vivo correlations, protein binding
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-238415DOI: 10.1002/ddr.21226ISI: 000344395100001PubMedID: 25315512OAI: oai:DiVA.org:uu-238415DiVA: diva2:772956
Available from: 2014-12-17 Created: 2014-12-12 Last updated: 2017-12-05Bibliographically approved

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