Platinum levels in human erythrocytes following intravenous administration of cisplatin: importance of erythrocytes as a distribution site for platinum species.

Recent reports of the extent of uptake of cisplatin and possible biotransformation products of cisplatin by red blood cells of humans receiving this drug have been conflicting. In vitro and in vivo studies of the platinum content of washed red blood cells following exposure to cisplatin have been conducted. Low levels of platinum were found in the red cell lysate of the erythrocytes of humans receiving cisplatin. The platinum was primarily associated with red cell lysate and little, if any, platinum appeared to be associated with the cell membrane. The in vivo studies indicated that the intracellular platinum levels are rapidly achieved following cisplatin administration and the platinum concentration appears to be linearly related to the administered dose. However, the fraction of platinum found within the erythrocytes is slight, representing only about 1 per cent of the administered dose. In light of the reactivity of cisplatin with compounds containing divalent sulphur and the millimolar glutathione levels present within erythrocytes, it is unlikely that the platinum released from the red blood cell is in the form of cisplatin. Therefore, it is doubtful that the red blood cell is a major site for cisplatin distribution and the anticancer activity of the platinum released from red blood cells is questionable.