| Autor: |
Demant EJ; Department of Medical Biochemistry and Genetics, The Panum Institute, University of Copenhagen, Denmark., Friche E |
| Jazyk: |
angličtina |
| Zdroj: |
Biochemical pharmacology [Biochem Pharmacol] 1998 Nov 01; Vol. 56 (9), pp. 1209-17. |
| DOI: |
10.1016/s0006-2952(98)00255-x |
| Abstrakt: |
A multidrug-resistant Ehrlich ascites tumor cell line (EHR2/DNR+) was used to examine the membrane transport kinetics of lipophilic anthracycline derivatives in the presence of serum albumin. We present a model for theoretical data analysis with consideration of drug-albumin complex formation. For a set of five derivatives (doxorubicin, daunorubicin, 4-demethoxydaunorubicin, 4'-deoxy-4'-iododoxorubicin, and 13-dihydro-4'-deoxy-4'-iododoxorubicin), data were given on the rates of diffusional drug uptake, and membrane permeability coefficients of the noncharged molecules were estimated. Both the initial rates and the steady-state levels of drug uptake were found to decrease by addition of BSA at concentrations ranging from 5 to 75 mg/mL. For each drug, this effect of serum albumin could be accounted for by the altered distribution between free and protein-bound drug molecules in the bulk aqueous medium. A good fit of theoretical accumulation curves to the experimental data was obtained. It was concluded that a mathematical simulation method makes it possible to predict the uptake characteristics of lipophilic anthracycline compounds into tumor cells under serum conditions. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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