Effect of cyclophosphamide pretreatment on the short-term disposition and biliary excretion of adriamycin metabolites in rat
- 1 December 1982
- journal article
- research article
- Published by Springer Nature in Cancer Chemotherapy and Pharmacology
- Vol. 10 (1), 11-15
- https://doi.org/10.1007/bf00257229
Abstract
Summary The effect of pretreatment with cyclophosphamide 180 mg/kg upon the short-term disposition of adriamycin in anesthetized rat 4 days later was studied. There was a significant decrease in plasma adriamycin clearance, from 125 to 48 ml/min/kg, and a significant decrease in the apparent volume of the peripheral compartment of adriamycin distribution, from 51.7 to 25.6 l/kg, in cyclophosphamide-pretreated as against control rats. Biliary excretion of adriamycin over 2.5 h was increased significantly by 114% in cyclophosphamide-pretreated rats and there was a small but nonsignificant increase in biliary adriamycinol excretion and a decrease in excretion of adriamycin aglycones. Cyclophosphamide pretreatment was associated with an 83% increase in bile flow. Cyclophosphamide pretreatment had no significant effect upon the utilization of adriamycin or upon the formation of adriamycin metabolites by rat isolated hepatocytes. The results suggest that NADPH-cytochrome P-450 reductase, which is decreased 40% by cyclophosphamide pretreatment, is not rate-limiting in elimination of adriamycin. Biliary excretion of adriamycin is increased when plasma adriamycin clearance is decreased, suggesting that cyclophosphamide pretreatment affects a pathway besides biliary excretion that is responsible for the short-term removal of adriamycin from plasma.Keywords
This publication has 23 references indexed in Scilit:
- Iron-EDTA stimulated reduction of indicine N-oxide by the hepatic microsomal fraction, isolated hepatocytes, and the intact ratBiochemical Pharmacology, 1982
- Determination of adriamycin (doxorubicin) and related fluorescent compounds in rat lymph and gall by high-performance liquid chromatographyJournal of Chromatography A, 1981
- Inhibition of NADPH-cytochrome P450 reductase by cyclophosphamide and its metabolitesBiochemical and Biophysical Research Communications, 1981
- Reversed-phase liquid chromatographic determination of plasma levels of adriamycin and adriamycinolJournal of Chromatography B: Biomedical Sciences and Applications, 1979
- Rapid determination of doxorubicin and its fluorescent metabolites by high pressure liquid chromatographyAnalytical Biochemistry, 1979
- NADPH cytochrome P-450 reductase activation of quinone anticancer agents to free radicals.Proceedings of the National Academy of Sciences, 1979
- N-demethylation of aminopyrine in vivo and in the isolated hepatocyte of the ratBiochemical Pharmacology, 1979
- Biliary disposition of adriamycinClinical Pharmacology & Therapeutics, 1977
- THE PERSISTENCE OF ADRIAMYCIN IN MAN AND RATBritish Journal of Clinical Pharmacology, 1974
- Comparative pharmacokinetics of daunomycin and adriamycin in several animal species.1972