The penetration of misonidazole and desmethylmisonidazole into brain tumours and other central nervous system tissues in man

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Abstract
The concentration of drug after oral administration of 1 g misonidazole to patients undergoing neurosurgery was studied in samples taken from intracerebral tumors, normal brain, CSF and brain tumor cyst fluid. A total of 31 patients yielded samples at various times 2-8 h after drug administration. Results show a considerable range of tumor/plasma percentages, but from .apprx. 2-5 h after drug administration this averaged 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 another 11 patients showed a similar range of tumor 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 tumors also had much lower concentrations than macroscopically viable tissue. The results are discussed in terms of their clinical relevance to sensitizer studies on patients with brain tumors with drugs of different lipophilicities.