ALTERATIONS IN ADRIAMYCIN EFFICACY BY PHENOBARBITAL

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  • 1 January 1976
    • journal article
    • research article
    • Vol. 36  (10) , 3803-3806
Abstract
Adriamycin dosage should be reduced in patients with impaired liver function, since adriamycin disposition is influenced by liver metabolism and biliary excretion. It follows that drugs that increase the metabolism or excretory capacity of the liver may decrease adriamycin concentrations to suboptimal values. Adriamycin metabolism was studied in mice pretreated with phenobarbital (75 mg/kg i.v.) by injection. After an i.v. dose of adriamycin (30 mg/kg i.v.), plasma fluorescence due to drug and metabolites was less and disappeared at a greater rate in phenobarbital pretreated mice than control animals. When extracted with chloroform:isopropyl alcohol (1:1), livers from the phenobarbital pretreated group yielded a greater concentration of aglycones. Experiments with liver microsomes confirmed that aglycone production occurred at a more rapid initial rate in phenobarbital induced livers. No increase in aldoketo reductase (daunorubicin reductase) activity was noted. Phenobarbital pretreated mice, inoculated i.p. with 1 million L1210 cells and then treated with adriamycin (6 mg/kg i.v.), had significantly lower survival than controls (P < 0.01). Phenobarbital affects the disposition of adriamycin by microsomal enzyme induction. Drugs that induce microsomal enzymes should not be used concurrently with adriamycin if optimal drug efficacy is desired.