Penetration of etoposide into human malignant brain tumors after intravenous and oral administration - PubMed (original) (raw)

Comparative Study

doi: 10.1007/BF00686001.

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Comparative Study

Penetration of etoposide into human malignant brain tumors after intravenous and oral administration

K Kiya et al. Cancer Chemother Pharmacol. 1992.

Abstract

Penetration of etoposide into the cerebrospinal fluid, brain tumor, and brain tissue after intravenous administration was investigated in patients presenting with malignant brain tumors. A relatively low dose (55-65 mg/m2) was used to compare intravenous with oral administration. High-performance liquid chromatography with fluorescence detection was used to evaluate drug levels. Plasma and cerebrospinal fluid levels of etoposide after oral administration (50-150 mg/day) were also studied so as to determine the adequate oral dose for the treatment of malignant brain tumors. The peak plasma concentration after intravenous administration ranged from 7.01 to 10.47 micrograms/ml, varying in proportion to the injected dose, whereas that after oral administration was lower, namely, 1.44-4.99 micrograms/ml, and was unstable when the oral dose was 150 mg daily. The peak cerebrospinal fluid level following either intravenous or oral administration was much lower than the plasma concentration and was influenced by the peak plasma level and the sampling site. The etoposide concentration in cerebrospinal fluid taken from the subarachnoid space and ventricle of patients displaying no tumor invasion and of those presenting with meningeal carcinomatosis and in cerebrospinal fluid taken from the dead space after tumor resection was 0.7% +/- 0.5%, 3.4% +/- 1.0%, and 7.2% +/- 8.5%, respectively, of the plasma concentration. Serial oral administration did not result in the accumulation of etoposide in cerebrospinal fluid. The tumor concentration (1.04-4.80 micrograms/g) was 14.0% +/- 2.9% of the plasma level after intravenous administration, was related to the injected dose, and was approximately twice the concentration detected in the brain tissue. Therefore, a relatively low dose of etoposide injected intravenously penetrates the brain tumor at an efficacious concentration. Our results indicate than an oral dose of 100 mg etoposide be given for malignant brain tumors, as limited penetration of the drug into the intracranial region was observed.

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References

    1. J Clin Oncol. 1984 May;2(5):432-7 - PubMed
    1. Cancer Treat Rep. 1985 Jun;69(6):603-5 - PubMed
    1. Semin Oncol. 1990 Feb;17(1 Suppl 2):49-53 - PubMed
    1. Eur J Cancer Clin Oncol. 1988 Feb;24(2):131-5 - PubMed
    1. J Neurooncol. 1987;4(4):397-401 - PubMed

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