Differences in accumulation of anthracyclines daunorubicin, doxorubicin and epirubicin in rat tissues revealed by immunocytochemistry.
Although anthracycline antibiotics daunorubicin (DR), doxorubicin (DX), and epirubicin (ER) possess minor differences in their chemical structures, large differences are noted in their clinical use, as well as in cellular and plasma pharmacokinetic parameters in vivo. Immunocytochemistry for DR, DX, or ER was developed using an anti-DR monoclonal antibody (ADM-1-11), which has been demonstrated to react equally well with each of the three drugs, and therefore it was used for comparing their accumulation in several rat tissue cells after a single i.v. injection of each drug. In the kidney, immunoreactivity for each drug was distributed in essentially the same pattern and in the same strength 2 h after injection, but quite differently distributed in kidney cells thereafter, so that at 120-h post-injection significant amounts of DX and ER remained, but DR had almost completely vanished. Similar patterns of accumulation were observed in cells of other tissues including the pancreas, hair follicle, and stomach, with the exception of the intestine in which none of the three drugs remained after 120 h. These results appear to be supported by previous pharmacokinetic studies on the anthracyclines. The mechanism for such differences among the three drugs remains obscure, but the hydroxyl group at C-14 of DX and ER molecule might be related to the strong propensity of DX and ER to accumulate in tissue cells. The present results should contribute to the understanding of the mechanisms of the differences in the pharmacokinetics, as well as the possibly in anti-tumor activities of the anthracyclines.
Shin
Masashi
M
Department of Applied Life Science, Faculty of Biotechnology and Life Science, Sojo University, Kumamoto, Japan.
Matsunaga
Hayato
H
Fujiwara
Kunio
K
D000818:Animals; D018943:Anthracyclines / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D003630:Daunorubicin / Q000493:pharmacokinetics; D004317:Doxorubicin / Q000493:pharmacokinetics; D015251:Epirubicin / Q000493:pharmacokinetics; D007150:Immunohistochemistry; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D018943:Anthracyclines; D000970:Antineoplastic Agents; D015251:Epirubicin; D004317:Doxorubicin; D003630:Daunorubicin