Drug interactions affecting the elimination of doxorubicin in the rat

Radioactive 14C-doxorubicin (10 mg/kg iv; 2 microCi/kg) disappeared rapidly from the plasma of anaesthetized male Sprague-Dawley rats. Radioactivity appeared in the bile within 5 to 7 min, reached a peak concentration in 10 to 15 min and declined rapidly thereafter for 150 min during which about 22% of the injected dose appeared in the bile. Tissue concentrations measured 10 min after injection were compared with tissue samples obtained at 150 min. Polyexponential analysis of the amount of doxorubicin remaining in the body (based upon the amount injected minus the cumulative amount excreted) suggested a two-compartment model. In acute studies, the injection of bromosulphophthalein (50 mg/kg) or rifampicin (53 mg/kg) 60 min after the injection of doxorubicin reduced the excretion of doxorubicin. The daily administration of phenobarbital (75 mg/kg X 3) increased the cumulative excretion of doxorubicin; the administration of CCl4 (1 ml/kg, ip) 24 hrs before the experiment reduced the cumulative excretion of doxorubicin.