Systemic chemotherapy for a primary germ cell tumor of the brain: a pharmacokinetic study.

Systemic administration of most chemotherapeutic agents has been assumed to be ineffective in the treatment of primary and metastatic brain tumors because these agents fail to cross the intact blood-brain barrier. However, agents which fail to penetrate the intact blood-brain barrier may penetrate it under conditions which include the presence of tumor in the central nervous system (CNS) and prior CNS irradiation. This paper reports the results of pharmacokinetic studies of bleomycin, cisplatin, and vinblastine in the CNS of a patient with a primary germ cell tumor of the brain who had received prior radiotherapy. Significant concentrations of bleomycin and cisplatin, but not of vinblastine, were reached in the cerebrospinal fluid (CSF) of the patient following iv administration. The area under the bleomycin CSF concentration times time curve was 25% of the area under the bleomycin plasma concentration times time curve. The areas under two cisplatin CSF curves were 50% and 155% of the areas under the corresponding free cisplatin plasma curves. Moreover, an objective response of the tumor to the chemotherapy was documented. This study provides evidence that, under certain circumstances, significant concentrations of cisplatin and bleomycin may be obtained in human CSF following systemic administration and that it may be possible to treat primary or metastatic CNS tumors with agents effective against systemic tumor of the same histologic type.

Determination of platinum in serum and ultrafiltrate by flameless atomic absorption spectrophotometry.

A graphite furnace atomic absorption spectrophotometric assay, capable of accurately determining nanogram amounts of platinum in serum and ultrafiltrate, was developed. A sample serum or ultrafiltrate was acidified with nitric acid and heated to destroy the protein-platinum bond. A measured excess of ammonium 1-pyrrolidinedithiocarbamate was added, and the platinum complex was extracted into isopropylacetone. The extract was injected into the graphite furnace. The sample was dried, charred, and atomized using optimal conditions. The resulting absorbance was used to determine the platinum content.

Analysis of carminomycin in human serum by fluorometric high-performance liquid chromatography.

A method is given for the determination of carminomycin (CMM) and a major metabolite carminomycinol (CMMOH) in serum from cancer patients after intravenous administration of carminomycin as the free drug. CMM and CMMOH are extracted from serum with chloroform, the extract evaporated and the residue dissolved in methanol. High performance liquid chromatography analysis utilized a C18 microBondapak reversed-phase column eluted with 0.1 mol/l acetate buffer (pH 4)-acetonitrile (60:40, v/v) with fluorescence detection. The assay is linear, reproducible, and precise with a limit of detection of 2 ng/ml. Representative serum levels of CMM and CMMOH in a cancer patients are presented.

Anthracycline assay by high-pressure liquid chromatography.

A general method of analysis of anthracycline concentrations was developed. Drug is extracted from plasma with organic solvent and separated from metabolites by high-pressure liquid chromatography on an aminocyanosilica column. Detection and quantitation are by the endogenous fluorescence of compounds having an intact tetracyclic ring structure. Limits of sensitivity are 5, 1, and 5 ng/ml of plasma for doxorubicin, carubicin, and marcellomycin, respectively. The assay can be used for studying the aldo-keto reductase and reductive glycosidase reactions with anthracyclines as the substrates and for the evaluation of the clinical pharmacology or pharmacodynamics of various doxorubicin analogs.

Pharmacokinetics of carminomycin in dogs and humans. Preliminary report.

Carminomycin was administered to four dogs and two human patients as a single intravenous dose. Plasma samples were obtained and assayed for carminomycin and carminomycinol by high pressure liquid chromatography with fluorescence detection. The plasma disappearance of carminomycin could be described by a three-compartment open model. Distribution was rapid and the apparent volume of distribution was greater than 100 l/m2 in both species. The terminal half-life of drug was 86 h in dogs and 20 h in humans. In both dogs and humans carminomycinol concentrations rapidly surpassed carminomycin levels, and terminal half-lives were longer than for the parent compound in the two species. Since carminomycinol has antitumor activity and host toxicity, this metabolite may play an important role in the efficacy and toxicity of carminomycin therapy.