作者: David G. Poplack , Jerry M. Collins , Cynthia Lester , John M. Strong
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摘要: The cerebrospinal fluid (CSF) and plasma pharmacokinetics of N,N',N"-triethylenethiophosphoramide (thiotepa), an alkylating agent used for treatment carcinomatous meningitis, were determined in rhesus monkeys order to assess the relative advantage intraventricular versus systemic administration drug. Following i.v. thiotepa dose 0.9 mg/kg (11 mg/sq m), peak levels parent drug reached approximately 1 microgram/ml. Thiotepa was rapidly equilibrated with lumbar ventricular CSF. Systemic, lumbar, exposure drug, measured as area under curve (AUC), similar all cases. After a 1-mg thiotepa, greater than 100 micrograms/ml. However, CSF at h after less 10 AUC nearly 100-fold route route; however, following delivery only 5% N,N',N''-Triethylenephosphoramide, active metabolite observed fluids, appeared have much slower total body clearance thiotepa. Comparison data obtained from monkey experiments patient meningeal disease supports use model pharmacokinetics. presented indicate that there is no doses currently clinical trials.