[Effect of phenobarbital and SKF 525-A on the toxic and therapeutic action of adriamycin in mice with Ehrlich ascites cancer].

The toxic action of adriamycin (AD) in mice with the ascitic Ehrlich carcinoma was reduced by preliminary administration of phenobarbital (PB), an inductor of liver monooxygenases, and was increased after administration of SKF 525-A, an inhibitor of this enzymatic system. PB and SKF decrease the therapeutic action of AD. Incidentally, induction or inhibition of the liver enzymes was equivalent to the decrease in the AD dose in mice with the intact liver. It was also shown that the essence of PB and SKF influence on the AD therapeutic effect is its action on liver monooxygenases activity and not the interaction between PB or SKF and AD or the change of AD sensitivity of tumour cells. The possible role of cytochrome P-450 in manifestation of the AD toxic and therapeutic activity is discussed. The authors believe that for prevention of AD toxicity in patients with liver disorders the treatment following stimulation of the liver metabolic activity up to the normal liver level may be effective.