Summary
The penetration of 12 commonly used anticancer agents through the blood-brain barrier (BBB) was measured in a rat model using a single-injection tissue-sampling technique. Two of the tested drugs penetrated the barrier, but only to a limited extent. Entry of the drugs into the brain tissue critically depends on molecular weight and lipophilia of the respective test compound. For drugs with a molecular weight of less than 500, BBB simply behaves like an oil/water interphase, whereas drugs with a molecular weight greater than 500 are practically excluded from transport through the BBB even if they show a favourable oil/water partition coefficient. However, permeability of cytostatics was strongly increased if short chain alkylglycerols, up to final concentrations of about 0.3 mol/l were added to the injected solution. Under these conditions the Brain-Uptake-Index (BUI) reached values up to about 50% (cyclophosphamide), depending on lipid solubility and molecular dimension of the respective test compound and the alkyl chain length of the glycerol derivative.
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Abbreviations
- BUI:
-
Brain-Uptake-Index
- ET-18-OCH3 :
-
1-Octadecyl-2-Methyl-rac-Glycerin-3-Phosphocholin
- Log p:
-
Logarithmus des Öl/Wasser-Verteilungskoeffizienten
- PG:
-
1-0-Pentyl-rac-Glycerin
- T M :
-
Phasenumwandlungstemperatur (Hauptumwandlung)
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Unger, C., Eibl, H., von Heyden, H.W. et al. Blut-Hirnschranke und Penetration von Zytostatika. Klin Wochenschr 63, 565–571 (1985). https://doi.org/10.1007/BF01733202
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DOI: https://doi.org/10.1007/BF01733202