Identification and kinetics of a beta-glucuronide metabolite of SN-38 in human plasma after administration of the camptothecin derivative irinotecan

摘要: Irinotecan (7-ethyl-10-{4-[1-piperidino]-1-piperidino}carbonyloxycamptothecin), also known as CPT-11, is a promising semi-synthetic derivative of camptothecin with significant activity against range tumour types. The pharmacokinetic behaviour its principal and presumedly active metabolite, SN-38 (7-ethyl-10-hydroxycamptothecin), displays wide inter-patient variation. During the high-performance liquid chromatographic (HPLC) analysis plasma samples collected from patient given we observed several unidentified peaks that were not present in pre-infusion samples. In this paper describe manner which one these was determined to be β-glucuronide SN-38. total concentrations metabolite quantified following digestion β-glucoronidase found greater than those studied. elimination phases concentration profile glucoronide parallel, suggesting transformation glucuronide rate-limiting step could play key role pharmacokinetics.