Investigation of the enterohepatic recirculation of Adriamycin and its metabolites by a linked-rat model

Cancer Chemotherapy and Pharmacology
K Behnia, M Boroujerdi

Abstract

We investigated the possible role of enterohepatic recirculation in prolongation of the half-life of elimination for Adriamycin, a commonly prescribed anticancer agent. We sought to determine whether enterohepatic recirculation of Adriamycin and its metabolites occurs using a linked-rat model. Two rats, a donor and a receiver, were linked via a catheter from the bile duct of the donor rat to the duodenum of the receiver. Control experiments were conducted with intact rats (without a bile duct cannula, control A) in order to estimate the half-life of elimination and with bile duct-cannulated rats (control B) to determine the amounts of Adriamycin and its metabolites in the bile. [14C-14]-Adriamycin was injected intravenously via the femoral vein to control A, control B and donor rats. The biological half-life of Adriamycin in the intact rats (control A, 10 h) was significantly higher than in the bile-duct-cannulated rats (control B, 4 h). The cumulative amount of Adriamycin and its metabolites excreted in the urine of the control A rats was also greater than from control B rats, indicating higher levels of the drug in their systemic circulation. Biological samples (bile, urine, plasma, blood cells and the major organs heart, liv...Continue Reading

Citations

Apr 10, 2008·Liver International : Official Journal of the International Association for the Study of the Liver·Leda RoncoroniMaria Teresa Bardella
Sep 9, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Henk VisscherUNKNOWN Canadian Pharmacogenomics Network for Drug Safety Consortium
Jun 18, 2002·The Journal of Pharmacology and Experimental Therapeutics·Jean-Francois MarierMurray P Ducharme

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