pyrimidinones and damvar

The pharmacokinetics of granulated Damvar (delta-(2-amino-6-hydroxy-3,4-dihydro-4-oxo-5-pyrimidinyl) valeric acid) after a single oral dose of 1000 mg was studied in 10 subjects with neoplastic disease. The rate of Damvar absorption from the digestive tract is not very fast. Maximal serum levels (13.5 micrograms/ml) were recorded 3 h after administration with minor interpersonal variations. The time course of Damvar serum concentrations coincides with its distribution in a two-compartmental pharmacokinetic model with biological half-life of 9.72 +/- 0.84 h. Only a small amount of Damvar is eliminated in urine during a period of 24 h (3.1% of the administered dose). Its renal clearance is also low (0.05 ml/s). The analysis of Damvar excretion in urine shows that kidneys play a minor role in its elimination from the body. Therefore the attention should be concentrated on the effect of Damvar administration in patients with disturbed metabolic functions.

Topics: Administration, Oral; Aged; Antineoplastic Agents; Female; Half-Life; Humans; Kidney; Kinetics; Male; Mathematics; Middle Aged; Neoplasms; Pyrimidinones

The present paper deals with the effect of Damvar on hemopoiesis. The test of formation of hemopoietic splenic colonies (CFU-S) was used in mice, the peripheral blood picture and bone marrow differential after long-term administration of Damvar was tested in rats and dogs. The bone marrow cells from mice after a single dose of Damvar or cells incubated with Damvar in vitro showed no reduction of colony-forming activity. A single dose or repeated variable doses of Damvar, or combined administration of Damvar and Cyclophosphamide in some cases influenced the number of CFU-S in irradiated mice following transplantation of normal murine bone marrow cells. A number of CFU-S lower than 75% of the control count was never found. The application of Damvar to rats and dogs caused no significant changes in their blood pictures and bone marrows.

Topics: Animals; Antineoplastic Agents; Bone Marrow; Bone Marrow Transplantation; Colony-Forming Units Assay; Dogs; Female; Hematopoiesis; Male; Mice; Pyrimidinones; Rats; Transplantation, Homologous

The effects of azathioprine, either alone or combined with delta-(2-amino-6-hydroxy-3,4-dihydro-4-oxo-5-pyrimidinyl)-valeric acid (VUFB-9777, Damvar) on serum antibody formation was studied in mice. The immunosuppressive effect of azathioprine depended on the regimen of administration. VUFB-9777 alone produced no immunosuppressive effect but markedly enhanced that of azathioprine.

Topics: Animals; Antibody Formation; Azathioprine; Drug Interactions; Female; Hemagglutination Tests; Hemolysis; Mice; Pyrimidinones; Sheep; Time Factors

Topics: Antineoplastic Agents; Pyrimidinones; Spectrophotometry

The new cytostatic drug Damvar, delta-(2-amino-6-hydroxy-3,4-dihydro-4-oxo-5-pyrimidinyl)valeric acid, is not effective in La leukemia system. Damvar given in combination with 5-fluorouracil enhanced the anti-La effect of 5-Fu. There was also enhancement of the antileukemic effect of suboptimal and optimal doses of cyclophosphamide with the addition of Damvar.

Topics: Animals; Antimetabolites, Antineoplastic; Cyclophosphamide; Drug Synergism; Drug Therapy, Combination; Fluorouracil; Leukemia, Experimental; Male; Mice; Mice, Inbred C57BL; Pyrimidines; Pyrimidinones

Damvar, the delta-(2-amino-6-hydroxy-3,4-dihydro-4-oxo-5-pyrimidinyl) valeric acid, administered alone s. c. or i. p., has no effect on L1210 leukemia. In DBA2 mice with L1210, Damvar administered in combination with 5-fluorouracil, or with 6-mercaptopurine, or with cyclophosphamide, in optimal doses, enhances or intensifies the antileukemic effects of the above cytostatics.

Topics: Animals; Antineoplastic Agents; Cyclophosphamide; Drug Therapy, Combination; Female; Fluorouracil; Leukemia L1210; Male; Mercaptopurine; Mice; Pyrimidinones

In experiments performed in mice, Adriamycin (15 mg/kg i. p.) produced serious damage of the heart muscle. Damvar (2 x 200 mg/kg orally) a new cytostatic drug combined with Adriamycin decreased conspicuously its cardiotoxicity.

Topics: Animals; Antineoplastic Agents; Doxorubicin; Drug Interactions; Drug Therapy, Combination; Heart Diseases; Male; Mice; Pyrimidinones

Topics: Administration, Oral; Adult; Aged; Antimetabolites; Female; Humans; Male; Middle Aged; Neoplasms; Pyrimidinones

In experiments on H mice and Wistar rats it was found that radioactivity was excreted after subcutaneous injection of Damvar-14C preponderantly in urine, and after oral administration, in faeces. After subcutaneous injection the urinary excretion set on very fast. After subcutaneous injection of Damvar-14C to H mice with Crocker's ascitic sarcoma S 180, peak radioactivity values were found in the majority of organs, blood, and ascitic fluid at hour 1 after injection; in the kidneys the peak value appeared as late as at hour 6. The renal levels were conspicuously higher than the other ones. Relatively high radioactivity levels were found in the ascitic fluid, skin, and blood. After oral administration the radioactivity levels in all organs, blood, and ascitic fluid culminated at hour 3 after ingestion. The highest levels after oral administration were likewise found in the kidneys and ascitic fluid. With the exception of the kidneys, blood, and skin, the peak values of specific radioactivity in organs were equally high or even higher after oral than after subcutaneous administration of the labeled substance. Furthermore, it was found that after administration of Damvar-14C to rat mothers the transfer of radioactivity into the milk and then into the sucklings was very slight, and so was the penetration of radioactivity into fetuses.

Topics: Administration, Oral; Animals; Female; Injections, Subcutaneous; Kinetics; Maternal-Fetal Exchange; Mice; Milk; Pregnancy; Pyrimidinones; Rats; Sarcoma 180; Tissue Distribution