The pharmacokinetic interaction between irinotecan and sunitinib
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The previous clinical trials found that the co-administration of irinotecan with sunitinib exhibited a synergistic antitumor effect. In the current study, we aimed to investigate whether the synergistic effect is related to a potential pharmacokinetic interaction between sunitinib and irinotecan. The inhibitory effects of sunitinib on SN-38 glucuronidation were determined by measuring the formation rates for SN38 glucuronide using recombinant human UGT isoforms and human liver microsomes (HLMs) in the absence or presence of sunitinib. Our data indicated that sunitinib exhibited competitive inhibition against SN-38 glucuronidation by UGT1A1, but inhibitory effects of sunitinib were weak in pooled human liver microsomes (HLMs) (Ki = 119.00 μM) and recombinant UGT1A1 (Ki = 42.71 μM). Our further prediction study partly explains the possible mechanism of synergistic antitumor activity of sunitinib and irinotecan in the combined treatment and provides a basis for design of clinical studies for the development and optimization of this combination.
KeywordsSunitinib Irinotecan SN-38 Pharmacokinetic interaction
This study was financially supported by the National Key Research and Development Program of China (2017YFC1702006), the Dalian Science and Technology Innovation Foundation (2018J13SN114). All funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Compliance with ethical standards
Conflict of interest
All the authors declare that they have no conflict of interests.
This article does not contain any studies with human participants or animals performed by any of the authors.
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