Time dependency in plasmatic protein binding of cisplatin.

The rate of cisplatin binding on proteins was measured in plasma collected from the same patients at several different times of the day. Statistical analysis showed that binding on plasma followed a circadian rhythm with the acrophase occurring around 4 PM. The amplitude of the apparent circadian variation of the binding depends on each patient (mean value, 11%). The binding capacity of plasma was also found to be time-dependent when the patients were prehydrated. The existence of a circadian rhythm in total protein concentration of the plasma could explain the observed results. Since cisplatin is bound more quickly on proteins in the afternoon, the circulating levels of free cisplatin must be lower when the injection is given at this time of day and this may partly explain the reduction in nephrotoxicity for some patients when cisplatin is injected in the afternoon.