PT  - JOURNAL ARTICLE
AU  - P Dodion
AU  - S R Akman
AU  - J M Tamburini
AU  - C E Riggs, Jr
AU  - O M Colvin
AU  - N R Bachur
TI  - Interactions between cyclophosphamide and doxorubicin metabolism in rats. II. Effect of cyclophosphamide on the aldoketoreductase system.
DP  - 1986 Apr 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 271--274
VI  - 237
IP  - 1
4099  - http://jpet.aspetjournals.org/content/237/1/271.short
4100  - http://jpet.aspetjournals.org/content/237/1/271.full
SO  - J Pharmacol Exp Ther1986 Apr 01; 237
AB  - Under anaerobic conditions, in comparison to liver microsomes obtained from normal controls, liver microsomes obtained from rats pretreated with cyclophosphamide formed significantly less 7-deoxydoxorubicinol aglycone (P less than or equal to .05), whereas the disappearance of doxorubicin and the formation of 7-deoxydoxorubicin aglycone were unaffected. When directly investigated, the reduction of 7-deoxydoxorubicin aglycone to 7-deoxydoxorubicinol aglycone by microsomes was inhibited by cyclophosphamide pretreatment. Liver cytosols from controls and cyclophosphamide-treated rats reduced daunorubicin to daunorubicinol and 7-deoxydoxorubicin aglycone to 7-deoxydoxorubicinol aglycone at the same rate, which indicates the lack of effect of cyclophosphamide pretreatment on the cytosolic aldoketoreductase. The results suggest the existence of a microsomal carbonyl reduction system for anthracycline antibiotics and indicate that cyclophosphamide does affect the metabolism of doxorubicin; in rats, this interaction results only in an alteration of the relative concentrations of presumably inactive metabolites, the 7-deoxyaglycones. The importance of these findings for the pharmacological interaction between doxorubicin and cyclophosphamide in humans remains to be investigated.