Stereoselectivity of iododoxorubicin reduction in various animal species and humans.
1. The excretion of iododoxorubicin in urine as the 13-dihydro derivative, iododoxorubicinol, is much greater in man than in rat, dog, rabbit and monkey. Iododoxorubicinol epimers in urine from man and the animal species after i.v. administration of iododoxorubicin, were quantified by h.p.l.c. 2. (13R)-Iododoxorubicinol was not detectable in rat, dog and human urine and accounted for no more than 0.15% dose in urine of 1/3 rabbits and 3/3 monkeys. (13S)-Iododoxorubicinol in human urine amounted to 5.6% dose, whereas in rat only 0.01% dose and in monkey only 0.91% dose was found. 3. As for idarubicin, the in vivo reduction of iododoxorubicin is highly stereoselective, giving the (13S)-epimer almost exclusively. Erythrocyte ketone reductases may account for the higher formation of (13S)-iododoxorubicinol in man.
Strolin Benedetti
M
M
Farmitalia Carlo Erbs, Research and Development-Erbamont Group, Milan, Italy.
Fraier
D
D
Pianezzola
E
E
Castelli
M G
MG
Dostert
P
P
Gianni
L
L
D000818:Animals; D004285:Dogs; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000652:urine; D005260:Female; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013237:Stereoisomerism
C062054:4'-iodo-4'-deoxydoxorubicinol; C053044:4'-deoxy-4'-iododoxorubicin; D004317:Doxorubicin