DETERMINATION OF UNBOUND PLATINUM AFTER OXALIPLATIN ADMINISTRATION - COMPARISON OF CURRENTLY AVAILABLE METHODS AND INFLUENCE OF VARIOUS PARAMETERS

Variations in plasma protein binding may have profound effects on both disposition and activity of drugs, especially for those which are tig htly bound to proteins, such as anticancer platinum derivatives. Metho ds of separation of the non-protein-bound fraction and some technical parameters may influence the results. We have compared ultrafiltration and ultracentrifugation, as well as the effect of potentially interfe ring factors, upon the determination of the plasma unbound platinum fr action after oxaliplatin administration to cancer patients. Ultrafiltr ation and ultracentrifugation provided very closely correlated results , so that either technique can be used. The ultrafiltration cut-off (3 000-30 000 Da) devices, the type of tube for blood sampling and the ty pe of anticoagulant (none, lithium heparinate or EDTA) did not influen ce the results markedly. In contrast, results were greatly influenced by freezing: erratic results were obtained on thawed plasmas when comp ared with those on fresh serum or plasma. Consequences may be importan t in usual practice, since many pharmacokinetic studies are carried ou t in multicentric trials with plasma processing centralized in one ref erence laboratory. The methods for the determination of protein-drug b inding should be standardized and guidelines elaborated where optimal conditions for each type of binding assay are given. [(C) 1998 Rapid S cience Ltd.].