Effect of hyperthermia on the in vitro metabolism of doxorubicin.

The effect of hyperthermia on the uptake and metabolism of doxorubicin (ADM) was studied in in vitro systems. ADM uptake in rat liver slices was not affected by increasing the temperature from 37 degrees C to 43 degrees C. In rat liver homogenates, the aerobic transformation of ADM was low and was not affected by hyperthermia. Approximately 90% of the parent drug remained unchanged after 60 minutes of incubation, and two metabolites, adriamycinol and a polar metabolite, were formed in small amounts. Under anaerobic conditions, ADM was quickly and extensively converted to two metabolites identified as 7-deoxyadriamycinol aglycone and 7-deoxyadriamycin aglycone. Whereas the disappearance of ADM and the formation of 7-deoxyadriamycin aglycone were not modified by the hyperthermic conditions, there was a slight but significant increase of the formation of 7-deoxyadriamycinol alycone (area under the concentration versus time curve in microM X minute: 216 +/- 24 at 37 degrees C; 235 +/- 24 at 39.5 degrees C; and 271 +/- 8 at 42 degrees C; P less than or equal to 0.05). However, the percentage of dA3 was not significantly different at the end of the incubation.