Clinical pharmacology of intrathecal methotrexate. II. An improved dosage regimen derived from age-related pharmacokinetics.
Cerebrospinal fluid (CSF)-antifolate concentration was analyzed in 100 specimens from 47 patients treated with intrathecal methotrexate (MTX) (12 mg/m2 of body surface area [BSA]). The drug concentrations varied 100-fold, with high levels associated with neurotoxicity and low levels with a poor response to therapy. CSF-MTX concentration was correlated directly with patient age, suggesting that a constant dose, regardless of age or BSA, should provide more consistent CSF-drug concentrations. In a subsequent study 25 patients treated with a conventional-dose schedule of 12 mg/m2 of BSA were compared with a matched group of 24 patients administered a constant dose of 12 mg. There was significantly less variability of drug levels in the CSF with the constant-dose method than with the dosage derived from BSA. It is recommended that patients between 3 and 40 years of age receive the same intrathecal dose rather than varying doses adjusted for patient BSA.
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001830:Body Surface Area; D002493:Central Nervous System Diseases / Q000188:drug therapy / Q000517:prevention & control; D002648:Child; D004334:Drug Administration Schedule; D006801:Humans; D007278:Injections, Spinal; D007938:Leukemia / Q000188:drug therapy*; D008727:Methotrexate / Q000008:administration & dosage* / Q000134:cerebrospinal fluid
D008727:Methotrexate