The penetration of misonidazole and desmethylmisonidazole into brain tumours and other central nervous system tissues in man.
The concentration of drug after oral administration of 1 g misonidazole to patients undergoing neurosurgery has been studied in samples taken from intracerebral tumours, normal brain, cerebrospinal fluid and brain tumour cyst fluid. A total of 31 patients yielded samples at various times 2-8 h after drug administration. Results show a considerable range of tumour/plasma percentages but from about 2-5 h after drug administration this averaged between 65-80%. Normal brain and CSF showed similar good penetration but drug entry into cyst fluid was lower (30-50%). A further study with desmethylmisonidazole given to 11 additional patients showed a similar range of tumour penetration but lower concentrations in CSF and cyst fluid (10-20%). Low values were also seen in some but not all of the normal brain tissue samples. Necrotic tumour also had much lower concentrations than macroscopically viable tissue. These results are discussed in terms of their clinical relevance to sensitiser studies on patients with brain tumours with drugs of different lipophilicities.
D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008920:Misonidazole / Q000031:analogs & derivatives / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D009593:Nitroimidazoles / Q000378:metabolism*; D013997:Time Factors
D009593:Nitroimidazoles; D008920:Misonidazole; C009997:desmethylmisonidazole