carubicin and dihydrocarminomycin

Carminomycin was administered to five patients at a dose of 7.5 mg/m2 twice weekly. Plasma and urine samples were obtained during two subsequent 72-hr periods following drug administration, and assayed for carminomycin (C) and carminomycinol (Col) by HPLC with fluorescence detection. Distribution of carminomycin was rapid and drug levels decreased below the detection limit (5 X 10(-9)M) within 24 hr. Carminomycinol appeared very quickly and surpassed carminomycin levels in 10 min-4 hr, disappearing very slowly, with a half-life of 40-98 hr. No major differences in pharmacokinetic behavior were found when comparing the five patients in this study with patients who received 18 mg/m2, as described in a previous report. After the second dose of carminomycin in the 7.5 mg/m2 twice weekly schedule, however, carminomycin pharmacokinetics were found to be altered in comparison with the first dose, the most pronounced difference being an increase in the t1/2 for Col from 65 +/- 28 to 173 +/- 81 hr.

Topics: Adult; Aged; Breast Neoplasms; Carubicin; Daunorubicin; Drug Administration Schedule; Female; Humans; Kinetics; Middle Aged

In 9 patients with advanced malignant disease who received carminomycin (CMM) in an i.v. bolus injection (dose 18 mg/m2), curves of plasma concentrations of CMM and carminomycinol (CMMOH), a metabolite, versus time were constructed. For determination of plasma concentrations, high pressure liquid chromatography was used. For CMM and CMMOH the median areas under the curves (AUC's) were 31 (range 4-57) X 10(-8) mol/Ql/hr (measured over 24 hr) and 100 (range 309-158) X 10(-8) mol/l/hr (measured over 48 hr) respectively. From the data an accumulation of CMMOH in patients receiving treatments separated by brief intervals ban be predicted (half-life time of plasma disappearance for CMMOH was 2 days). Clinical toxicity was lowest in those 3 patients showing the lowest AUC for both CMM and CMMOH.

Topics: Breast Neoplasms; Carubicin; Chromatography, High Pressure Liquid; Daunorubicin; Humans; Sarcoma; Soft Tissue Neoplasms; Time Factors

Carminomycin (CMN) was administered i.v. to 44 patients with a variety of nonhematological cancers every 4 weeks at doses of 15, 20, 22.5, and 25 mg/sq m. Granulocytopenia was the dose-limiting toxicity. The median granulocyte count for previously untreated patients receiving 22.5 mg/sq m was 0.962 cells/microliters, and for previously treated patients receiving 20 mg/sq m it was 0.420 cell/microliters. Moderate to severe phlebitis was associated with drug administration in 50% of cases. Nausea, vomiting, and alopecia were mild. Three of nine patients who received a total CMN dose of greater than or equal to 100 mg/sq m (mean, 132 mg/sq m) developed unexplained decreases in radionuclide cardiac ejection fraction, with one patient developing decreased QRS amplitude and congestive heart failure at a total dose of 160 mg/sq m. CMN is rapidly metabolized to carminomycinol. The elimination half-lives of CMN and carminomycinol are 6 to 10 and 50 hr, respectively. CMN was found to be a more potent inhibitor of human granulocyte-macrophage colony-forming units than was carminomycinol. Objective partial responses were seen in two of seven previously untreated patients with non-small cell lung cancer and one of three patients with squamous cell carcinoma of the head and neck previously untreated with chemotherapy.

Topics: Adult; Aged; Agranulocytosis; Carubicin; Colony-Forming Units Assay; Daunorubicin; Drug Evaluation; Female; Heart Diseases; Humans; Infusions, Parenteral; Male; Middle Aged; Neoplasms

Carminomycin, an antitumor antibiotic, and 13-dihydrocarminomycin, its main metabolite, were determined in the blood plasma of patients with highly efficient liquid chromatography and a fluorescent detector (lambda ex=492 nm, lambda em=538 nm). The liquid chromatograph manufactured by Spectro-Physics, model SP-8000, with Particyl Column 10/25 was used for the determination. The composition of the mobile phase of acetonitrile--0.1 M H3PO4 was 93:7 by the volume. The mobility speed was 2 ml/min. The retention time of carminomycin, rubomycin (used as the national standard) and dihydrocarminomycin was 6.8, 8 and 10.2 minutes, respectively. All three substances showed symmetrical peaks with high resolution. The early phase kinetics of carminomycin after its intravenous injection to the patients in a dose of 24 mg (18 mg/m2) is satisfactorily described by the diexponential equation. The pharmacokinetic parameters of carminomycin corresponding to the open two-compartmental system are presented. Highly efficient liquid chromatography may be used for the pharmacokinetic description of biotransformation of carminomycin and some other antibiotics of the anthracycline group.

Topics: Carubicin; Chromatography, Liquid; Daunorubicin; Humans; Kinetics; Spectrometry, Fluorescence

The experiments on albino mice treated with rubomycin, carminomycin or dihydrocarminomycin on its 5-fold intravenous administration in doses equal to similar portions of LD50 of the respective antibiotic on its use in a single dose showed that all the 3 antibiotics induced changes in the myocardium close by their character. The heart affections were evident from swelling of separate muscle fibers, degeneration of the myofibrils, homogenization, vacuolization and resorption of the sarcoplasma, pathological changes in the nuclei, atrophy of some muscle fibers. Rubomycin had the highest cardiotoxic effect. Then followed dihydrocarminomycin and carminomycin. All the antibiotics studied in the experiments with mice had mainly an inhibitory effect on the lymphoid hemopoiesis. The effect of carminomycin was the highest. The animal death during the injections and immediately after administrations of the antibiotics must be due to their suppressing effect on hemopoiesis. The deaths at more remoted periods must be due to the cardiotoxic effect of the antibiotics.

Topics: Animals; Antibiotics, Antineoplastic; Blood; Carubicin; Daunorubicin; Dose-Response Relationship, Drug; Heart; Injections, Intravenous; Kidney; Lethal Dose 50; Liver; Mice; Myocardium; Spleen; Time Factors