Comparative diffusion study of two nitrosoureas: carmustine and fotemustine in normal rat brain, human and rat brain biopsies.
In order to assess the apparent diffusion coefficient of two nitrosoureas (carmustine and fotemustine) in the brain, a model of planar diffusion was used in the rat brain and in rat and human brain biopsies. Drugs were deposed on the brain surface at a constant concentration for 30 min. At the end of the diffusion time, the concentration gradient was determined with microelectrodes using voltammetry at 5 different depths in the extracellular space of the gray matter (0-304 microns). Voltammetry with microelectrodes measured quantitatively intact drug in the brain extracellular space (CV 4% for the 2 drugs) in the range studied. The same procedure was used for human and rat brain biopsies which were held in a small cup. The apparent diffusion coefficients in living animals were 0.49 x 10(-6) cm2.s-1 for carmustine and 0.23 x 10(-6) cm2.s-1 for fotemustine; in human biopsies, they were 0.84 x 10(-6) cm2.s-1 for carmustine and 0.37 x 10(-6) cm2.s-1 for fotemustine. Significant differences in the apparent diffusion coefficients of the drugs were accounted for by the fact that the intracellular penetration of fotemustine was better than that of carmustine.
Meulemans
A
A
Faculté de Médecine Xavier-Bichat, Paris, France.
Giroux
B
B
Hannoun
P
P
Robine
D
D
Henzel
D
D
D000328:Adult; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism*; D002330:Carmustine / Q000493:pharmacokinetics*; D004058:Diffusion; D005260:Female; D006801:Humans; D008297:Male; D008839:Microelectrodes; D008875:Middle Aged; D009607:Nitrosourea Compounds / Q000493:pharmacokinetics*; D009943:Organophosphorus Compounds / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; C054368:fotemustine; D002330:Carmustine