ACNU delivery to malignant tumor tissue and serum--route of administration and combined use of phenobarbital

Since nitrosourea compounds as chemotherapeutic agent can cross the blood brain barrier, they are widely used in the treatment of malignant brain tumors. ACNU (3-[(4-amino-2-methyl-5-pyrimidinyl) methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride) has become a popular agent, as it is water-soluble and has shown potent effectiveness for treating gliomas. Only a few studies have ever been reported concerning the pharmacokinetics of ACNU in human brain tumors. Intra-arterial administration of chemotherapeutic agents has recently been paid special attention, because it is expected to be more effective than intravenous administration. On the other hand, phenobarbital as an anticonvulsant, widely used in clinical management of malignant brain tumor patients has been reported to reduce the toxicity of nitrosourea compounds by induction of hepatic microsomal enzyme relating to their metabolism. In this report, malignant brain tumor patients were divided into two groups; ACNU was administered either by internal carotid or intravenous route. ACNU concentrations in blood or tumor tissue following the administration were serially compared between these two groups. Patients were also divided into another two groups; ACNU was administered in combination with or without phenobarbital. Between these two groups, ACNU in concentrations in blood were serially compared in order to detect the influence of phenobarbital. ACNU concentrations in tumor tissues were measured at 5, 10, 15, 20, 25, 30, (40, 45, 50), 60 minutes after intravenous (IV) or internal carotid arterial (ICA) administration of ACNU (2-3 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)