{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:06:45Z","timestamp":1787771205352,"version":"build-2784847793"},"reference-count":32,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T00:00:00Z","timestamp":1664755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science","award":["20K07150"],"award-info":[{"award-number":["20K07150"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The purpose of this study was to evaluate the effects of NR1I2 (7635G&gt;A and 8055C&gt;T) and ABCB1 (1236C&gt;T, 2677G&gt;T\/A, and 3435C&gt;T) genetic polymorphisms on everolimus pharmacokinetics in 98 Japanese renal transplant patients. On day 15 after everolimus administration, blood samples were collected just prior to and 1, 2, 3, 4, 6, 9, and 12 h after administration. The dose-adjusted area under the blood concentration\u2013time curve (AUC0-12) of everolimus was significantly lower in patients with the NR1I2 8055C\/C genotype than in those with other genotypes (p = 0.022) and was significantly higher in male patients than female patients (p = 0.045). Significant correlations between the dose-adjusted AUC0-12 of everolimus and age (p = 0.001), aspartate transaminase (p = 0.001), and alanine transaminase (p = 0.005) were found. In multivariate analysis, aging (p = 0.008) and higher alanine transaminase levels (p = 0.032) were independently predictive of a higher dose-adjusted everolimus AUC0-12. Aging and hepatic dysfunction in patients may need to be considered when evaluating dose reductions in everolimus. In renal transplant patients, management using everolimus blood concentrations after administration may be more important than analysis of NR1I2 8055C&gt;T polymorphism before administration.<\/jats:p>","DOI":"10.3390\/ijms231911742","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T23:39:31Z","timestamp":1665272371000},"page":"11742","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of NR1I2 and ABCB1 Genetic Polymorphisms on Everolimus Pharmacokinetics in Japanese Renal Transplant Patients"],"prefix":"10.3390","volume":"23","author":[{"given":"Hironobu","family":"Yagishita","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Akita University Hospital, 1-1-1 Hondo, Akita 010-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Kagaya","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Akita University Hospital, 1-1-1 Hondo, Akita 010-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuru","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Urology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyuki","family":"Numakura","sequence":"additional","affiliation":[{"name":"Department of Urology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryohei","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Urology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuichiro","family":"Sagehashi","sequence":"additional","affiliation":[{"name":"Department of Urology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonori","family":"Habuchi","sequence":"additional","affiliation":[{"name":"Department of Urology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Satoh","sequence":"additional","affiliation":[{"name":"Center for Kidney Disease and Transplantation, Akita University Hospital, 1-1-1 Hondo, Akita 010-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7120-2425","authenticated-orcid":false,"given":"Masatomo","family":"Miura","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Akita University Hospital, 1-1-1 Hondo, Akita 010-8543, Japan"},{"name":"Department of Pharmacokinetics, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1111\/ajt.14215","article-title":"Association of clinical events with everolimus exposure in kidney transplant patients receiving low doses of tacrolimus","volume":"17","author":"Shihab","year":"2017","journal-title":"Am. 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