Direct administration of methotrexate into the central nervous system of primates: Part 1: Distribution and degradation of methotrexate in nervous and systemic tissue after intraventricular injection

摘要: Levels of methotrexate (MTX) measured by both 3H radioactivity and dihydrofolate reductase assays were determined in cerebrospinal fluid (CSF), plasma, urine, neural non-neural tissues at varying times after a single intraventricular injection into Cynomolgus monkeys (Macaca fascicularis). Clearance the MTX from CSF was rapid injection. A relatively constant level 3HMTX reached plasma 2 1/2 hours injection, about 30% dose excreted urine within 4 Maximum levels CNS obtained average concentrations 10(-6) M (moles/kg wet weight) maintained for up to 12 brain 24 Conversion non-MTX products detected between hours, tissue amount these increased with time. Regional distribution studies cerebrum showed U-shaped curve which closely followed 14C inulin distribution. Thus, deep cerebral less than brain, this suggests that treatment tumors may have variable results, partly due complex patterns.