Abstract
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 a range of tumour types. The pharmacokinetic behaviour of 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 of plasma samples collected from a patient given CPT-11, we observed several unidentified peaks that were not present in pre-infusion samples. In this paper we describe the manner in which one of these was determined to be a β-glucuronide of SN-38. The total plasma concentrations of this metabolite were quantified following digestion with β-glucoronidase and were found to be greater than those of SN-38 in the patient studied. The elimination phases of the plasma concentration profile of SN-38 and its glucoronide were parallel, suggesting that the transformation of SN-38 to the glucuronide is the rate-limiting step in the elimination of SN-38 and could play a key role in its pharmacokinetics.
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Rivory, L.P., Robert, J. Identification and kinetics of a β-glucuronide metabolite of SN-38 in human plasma after administration of the camptothecin derivative irinotecan. Cancer Chemother. Pharmacol. 36, 176–179 (1995). https://doi.org/10.1007/BF00689205
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DOI: https://doi.org/10.1007/BF00689205