In Vitro Binding and Partitioning of Irinotecan (CPT-11) and its Metabolite, SN-38, in Human Blood

The binding of CPT-11 and SN-38 to human plasma proteinswas studied by ultrafiltration at 37°C and pH 7.4. In plasma,CPT-11 was 66–60% bound in the range 100–4000ng/ml and SN-38 was 94–96% bound in the range50–200 ng/ml. At these concentrations the plasma bindingof CPT-11 was slightly saturable, but the plasma binding of SN-38was concentration-independent. Albumin was the main carrier ofCPT-11 and SN-38 in plasma. In blood, the binding of CPT-11 wasmoderate (80%), mainly to plasma proteins (47%) anderythrocytes (33%). The binding of SN-38 was high(99%) and most of SN-38 in blood was located in bloodcells (approximately 66%) The simulation of a grade 3hematotoxicity (according to National Cancer Institute's CommonToxicity Criteria grading) on the SN-38 blood distributionyielded an increase in fu (free fraction of drug in plasma) from1.05 to 2.08 and a decrease in CBl/CP from1.66 to 1.14 (both resulting from a decreased cellbinding).