Impact of Lenvatinib on OATP1B Activity in Patients with Hepatocellular Carcinoma

Impact of Lenvatinib on OATP1B Activity in Patients with Hepatocellular Carcinoma | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL British Journal of Clinical Pharmacology This is a preprint and has not been peer reviewed. Data may be preliminary. 12 May 2026 V1 Latest version Share on Impact of Lenvatinib on OATP1B Activity in Patients with Hepatocellular Carcinoma Authors : Ken Shiraiwa 0000-0003-2626-1711 [email protected] , Yoshio Sueshige [email protected] , Ryota Tanaka 0000-0002-8452-7971 [email protected] , Yosuke Suzuki 0000-0002-7092-4618 [email protected] , Ayako Oda [email protected] , Haruki Sato [email protected] , Daiki Toyama [email protected] , Hironori Abe [email protected] , Ryosuke Tatsuta 0000-0003-4949-362X [email protected] , Keiko Ohno [email protected] , and Hiroki Itoh [email protected] Authors Info & Affiliations https://doi.org/10.22541/authorea.15003181/v1 Under Review British Journal of Clinical Pharmacology Peer review timeline 10 views 6 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Aims: Lenvatinib (LEN) inhibits organic anion transporting polypeptide 1B1 (OATP1B1) in vitro, raising concerns about potential risk for transporter-mediated drug–drug interactions (DDIs). This study evaluated the in vivo impact of LEN on OATP1B activity in patients with hepatocellular carcinoma (HCC), using coproporphyrin-I (CP-I) as an endogenous biomarker. Methods: In this prospective, single-center, observational study, 26 patients with HCC treated with LEN were enrolled. Plasma CP-I concentrations were measured at baseline (pre-dose) and up to 24 hours after the first LEN dose. Patients were stratified by hepatic function (Child–Pugh A or B) and OATP1B1 genotype ( *15 carrier or non- *15 carrier). Temporal changes in CP-I concentrations were assessed using Dunnett’s test. Results: Plasma CP-I concentrations did not show a significant change from baseline at any of the measured time point following LEN administration, regardless of OATP1B1 genotype or hepatic function (all p > 0.220). Baseline CP-I concentration did not differ according to genotype (p = 0.948) but was significantly higher in Child–Pugh B patients than in Child–Pugh A patients (p = 0.013). Conclusions: LEN had no significant effect on OATP1B activity in patients with HCC, suggesting that the OATP1B1 inhibitory effect observed in vitro does not translate into clinically significant DDIs in this population. Reduced hepatic transporter function associated with underlying hepatic function impairment in HCC likely attenuates further drug-induced OATP1B inhibition. These findings indicate a low risk of OATP1B1-mediated DDIs during LEN therapy for HCC, although caution is warranted when extrapolating to patients with preserved hepatic function. Supplementary Material File (supplemental figure_bjcp_20260425.pdf) supplemental figure_bjcp_20260425 Download 54.25 KB Information & Authors Information Version history V1 Version 1 12 May 2026 Peer review timeline Under Review British Journal of Clinical Pharmacology 14 May 2026 Under Review Collection British Journal of Clinical Pharmacology Authors Affiliations Ken Shiraiwa 0000-0003-2626-1711 [email protected] Oita Daigaku - Hazama Campus, Yufu, Japan, 879-5593 View all articles by this author Yoshio Sueshige [email protected] Oita Daigaku - Hazama Campus, Yufu, Japan, 879-5593 View all articles by this author Ryota Tanaka 0000-0002-8452-7971 [email protected] Oita Daigaku - Hazama Campus, Yufu, Japan, 879-5593 View all articles by this author Yosuke Suzuki 0000-0002-7092-4618 [email protected] Oita Daigaku - Hazama Campus, Yufu, Japan, 879-5593 View all articles by this author Ayako Oda [email protected] Oita Daigaku - Hazama Campus, Yufu, Japan, 879-5593 View all articles by this author Haruki Sato [email protected] Oita Daigaku - Hazama Campus, Yufu, Japan, 879-5593 View all articles by this author Daiki Toyama [email protected] Oita Daigaku - Hazama Campus, Yufu, Japan, 879-5593 View all articles by this author Hironori Abe [email protected] Oita Daigaku - Hazama Campus, Yufu, Japan, 879-5593 View all articles by this author Ryosuke Tatsuta 0000-0003-4949-362X [email protected] Oita Daigaku - Hazama Campus, Yufu, Japan, 879-5593 View all articles by this author Keiko Ohno [email protected] Oita Daigaku - Hazama Campus, Yufu, Japan, 879-5593 View all articles by this author Hiroki Itoh [email protected] Oita Daigaku - Hazama Campus, Yufu, Japan, 879-5593 View all articles by this author Metrics & Citations Metrics Article Usage 10 views 6 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Ken Shiraiwa, Yoshio Sueshige, Ryota Tanaka, et al. Impact of Lenvatinib on OATP1B Activity in Patients with Hepatocellular Carcinoma. Authorea . 12 May 2026. DOI: https://doi.org/10.22541/authorea.15003181/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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