[Blood-brain barrier and the penetration of cytostatic drugs].
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.
Unger
C
C
Eibl
H
H
von Heyden
H W
HW
Krisch
B
B
Nagel
G A
GA
D000818:Animals; D000880:Anthraquinones / Q000378:metabolism; D000970:Antineoplastic Agents / Q000378:metabolism*; D001682:Biological Availability; D001761:Bleomycin / Q000378:metabolism; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply; D000440:Butanols / Q000378:metabolism; D002199:Capillary Permeability; D002250:Carbon Radioisotopes; D004075:Diglycerides / Q000378:metabolism; D004317:Doxorubicin / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008727:Methotrexate / Q000378:metabolism; D008942:Mitoxantrone; D010742:Phospholipid Ethers; D051381:Rats; D014316:Tritium
D000880:Anthraquinones; D000970:Antineoplastic Agents; D000440:Butanols; D002250:Carbon Radioisotopes; D004075:Diglycerides; D008244:Lysophosphatidylcholines; D010742:Phospholipid Ethers; D014316:Tritium; D001761:Bleomycin; C026659:edelfosine; D004317:Doxorubicin; D008942:Mitoxantrone; D008727:Methotrexate
Blut-Hirnschranke und Penetration von Zytostatika.