Characteristics of doxorubicin transport in human red blood cells

Abstract

The doxorubicin (Adriamycinn®) transport was investigated by measuring the net efflux of dororubicin from loaded erythrocytes into doxorubicin-free media at 37°C. The doxorubicin concentration in the cell water was kept low (5—10 μmol/l). The doxorubicin transport increased with increasing pH. The approx. pK_a of the doxorubicin amino group was 7.6 (37°C, ionic strength 0.15). Phloretin, 1-alcohols and local anaesthetics increased doxorubicin transport after the fashion of the effect of these drugs on membrane transport of lipophilic compounds. Several inhibitors of facilitated transport systems in erythrocytes did not affect doxorubicin transport. The calcium and magnesium concentration in the cell water (0—2 mmol/l) did not affect doxorubicin transport. It appears that doxorubicin transport in human erythrocytes takes place by free diffusion of the electrically uncharged (un protonated) doxorubicin molecule through the lipid domain of the cell membrane.

Key Words:

• Adriablastine
• Adriamycin
• 1-alcohols
• anthracyclines
• cancer chemotherapeutics
• free diffusion
• lipophilic compounds
• local anaesthetics
• phloretin