INTERACTION OF CAMPTOTHECIN DERIVATIVES WITH HUMAN PLASMA-PROTEINS INVITRO

The interactions of camptothecin (CPT) and its derivatives (CPT-11 and SN-38) with human plasma proteins (serum albumin (HSA) and alpha1-acid glycoprotein (alpha1-AGP)) were studied mainly by means of ultraviolet and fluorescence spectroscopy. The binding constants of lactone ring-opened forms (A form) of CPT and CPT-11 with HSA were larger than those of the intact lactone forms (L form). In the case of SN-38, there was no difference in the constants between A form and L form. The binding constant of CPT (A form) with HSA was larger than those of CPT-11 and SN-38. The presence of cisplatin, which is presumed to be coadministered with CPT derivatives, did not affect the interaction of CPT derivatives with HSA. Only L form of CPT-11 among the CPT derivatives examined interacted with alpha1-AGP, followed by quenching the fluorescence of alpha1-AGP.