ACNU動注療法における薬物動態について

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The intra-arterial administration of 3-[4-(amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU) was carried out in an attempt to achieve more effective delivery of ACNU to tumor cells with fewer systemic side effects. The concentration of ACNU in the blood, tumor tissue, and cerebrospinal fluid in 20 cases of malignant brain tumor was measured by high-performance liquid chromatography and the pharmacokinetics of ACNU were compared between intravenous and intra-arterial administration of the same dose of ACNU, using parameters of the mean concentration (MC) and area under the curve (AUC), and analyzed by the two compartment model. In three cases, intra-arterial administration of ACNU was carried out following blood-brain barrier (BBB) disruption. (1) The MC and AUC in the blood were not significantly different between the intravenous and intra-arterial administration groups. (2) On the other hand, both MC and AUC in the brain tumor tissue were significantly higher in the intra-arterial administration group than in the intravenous administration group. (3) The concentration of ACNU in the cerebrospinal fluid remained below 1 ng/ml in both groups. (4) Analysis using the two compartment model also revealed that the concentration of ACNU in tumor tissue was consistently higher in the intra-arterial administration group than in the intravenous administration group. (5) In the hyperosmolar BBB disruption group, MC and AUC in tumor tissue tended to be higher but varied among the cases. (6) No marked side effects due to the intra-arterial administration of ACNU were observed. This study indicates the superiority of intra-arterial ACNU ad-ministration to intravenous administration.
日本脳神経外科学会の論文
1987-06-15

ACNU動注療法における薬物動態について

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