1-METHYL-3-PROPYL-7-BUTYLXANTHINE, A NOVEL BIOCHEMICAL MODULATOR, ENHANCES THERAPEUTIC EFFICACY OF ADRIAMYCIN

We have screened xanthine derivatives for activity as novel biochemica l modulators by assay of their inhibitory effect on adriamycin efflux from tumor cells. Strong inhibition of adriamycin efflux was shown by some xanthine derivatives with various alkyl or oxoalkyl substituents at the 1-, 3- and 7-positions. 1-Methyl-3-propyl-7-butylxanthine (XT-7 7), which had the greatest inhibitory effect on adriamycin efflux in v itro among the compounds tested, potentiated adriamycin-induced antitu mor activity by causing an increase of adriamycin concentration in the tumor in vitro. Furthermore, XT-77 reduced the adverse drug reactions of adriamycin by decreasing the adriamycin concentrations in the hear t and the liver. Thus, the combination of XT-77 with adriamycin not on ly increased the antitumor activity of adriamycin, but also decreased the adverse drug reactions.