Transport mechanism of anthracycline derivatives in rat polymorphonuclear leukocytes: uptake of pirarubicin, daunorubicin and doxorubicin.

We performed experiments on the cis-inhibition and trans-stimulation effect on pirarubicin uptake in order to clarify the involvement of a carrier in the pirarubicin, daunorubicin and/or doxorubicin transport systems in rat polymorphonuclear leukocytes. The uptake of daunorubicin and doxorubicin was a saturable concentration-dependent process. Since the apparent kinetic constants, Michaelis constant (Km) and inhibition constant (Ki), were almost comparable, these drugs presented mutually competitive inhibition. Furthermore, the pirarubicin uptake by polymorphonuclear leukocytes was significantly elevated by increasing the preloaded amount of doxorubicin, indicating that there was a trans-stimulation effect on the pirarubicin transport in the leukocytes. These results suggest that carrier-mediated transport might be involved in the uptake of anthracycline derivatives, pirarubicin, daunorubicin and doxorubicin, by rat polymorphonuclear leukocytes.