{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T01:01:46Z","timestamp":1769907706770,"version":"3.49.0"},"reference-count":45,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T00:00:00Z","timestamp":1679443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01 GM146956-01"],"award-info":[{"award-number":["R01 GM146956-01"]}]},{"name":"Oklahoma Presbyterian Health Foundation Seed Grant","award":["R01 GM146956-01"],"award-info":[{"award-number":["R01 GM146956-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Impaired transport activity of hepatic OATP1B1 and OATP1B3 due to drug\u2013drug interactions (DDIs) often leads to increased systemic exposure to substrate drugs (e.g., lipid-lowering statins). Since dyslipidemia and hypertension frequently coexist, statins are often concurrently used with antihypertensives, including calcium channel blockers (CCBs). OATP1B1\/1B3-related DDIs in humans have been reported for several CCBs. To date, the OATP1B1\/1B3-mediated DDI potential of CCB nicardipine has not been assessed. The current study was designed to assess the OATP1B1- and OATP1B3-mediated DDI potential of nicardipine using the R-value model, following the US-FDA guidance. IC50 values of nicardipine against OATP1B1 and OATP1B3 were determined in transporter-overexpressing human embryonic kidney 293 cells using [3H]-estradiol 17\u03b2-D-glucuronide and [3H]-cholecystokinin-8 as substrates, respectively, with or without nicardipine-preincubation in protein-free Hanks\u2019 Balanced Salt Solution (HBSS) or in fetal bovine serum (FBS)-containing culture medium. Preincubation with nicardipine for 30 min in protein-free HBSS buffer produced lower IC50 and higher R-values for both OATP1B1 and OATP1B3 compared to in FBS-containing medium, yielding IC50 values of 0.98 and 1.63 \u00b5M and R-values of 1.4 and 1.3 for OATP1B1 and OATP1B3, respectively. The R-values were higher than the US-FDA cut-off value of 1.1, supporting that nicardipine has the potential to cause OATP1B1\/3-mediated DDIs. Current studies provide insight into the consideration of optimal preincubation conditions when assessing the OATP1B1\/3-mediated DDIs in vitro.<\/jats:p>","DOI":"10.3390\/pharmaceutics15031020","type":"journal-article","created":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T06:00:01Z","timestamp":1679464801000},"page":"1020","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Differential Preincubation Effects of Nicardipine on OATP1B1- and OATP1B3-Mediated Transport in the Presence and Absence of Protein: Implications in Assessing OATP1B1- and OATP1B3-Mediated Drug\u2013Drug Interactions"],"prefix":"10.3390","volume":"15","author":[{"given":"Ruhul","family":"Kayesh","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vishakha","family":"Tambe","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3821-6187","authenticated-orcid":false,"given":"Chao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"K\u00f6nig, J. 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