{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T01:58:22Z","timestamp":1788141502745,"version":"build-2803163510"},"reference-count":9,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T00:00:00Z","timestamp":1663027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,24]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Sodium zirconium cyclosilicate (SZC) is an oral, highly selective potassium binder approved for the treatment of hyperkalaemia in adults. SZC may change the absorption of co-administered drugs that exhibit pH-dependent bioavailability. This study evaluated whether the pharmacokinetic (PK) profiles of tacrolimus and cyclosporin were altered by concomitant SZC administration in healthy participants.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This was an open-label, randomised sequence, two-cohort crossover, single-centre study. Healthy adults were assigned to one of two cohorts: Cohort 1 (tacrolimus) received a single dose of tacrolimus 5\u00a0mg and tacrolimus 5\u00a0mg\u00a0+\u00a0SZC 15\u00a0g in a random order; Cohort 2 (cyclosporin) received a single dose of cyclosporin 100\u00a0mg and cyclosporin 100\u00a0mg\u00a0+\u00a0SZC 15\u00a0g in a random order. Primary PK endpoints were maximum observed blood concentration (Cmax) and area under the concentration\u2013time curve (AUC) from time zero to infinity (AUCinf). Differences in mean Cmax and AUCinf were analysed using a mixed effects model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Thirty participants in Cohort 1 and 29 in Cohort 2 completed the study. Tacrolimus exposure was lower with tacrolimus\u00a0+\u00a0SZC versus tacrolimus alone: Cmax geometric mean ratio (GMR) 71.10% [90% confidence interval (CI) 65.44\u201377.24], AUCinf 62.91% (55.64\u201371.13). Cyclosporin exposure was similar with cyclosporin\u00a0+\u00a0SZC compared with cyclosporin alone: Cmax GMR 102.9% (90% CI 96.11\u2013110.10), AUCinf 97.23% (92.93\u2013101.70).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Tacrolimus exposure was lower when co-administered with SZC 15\u00a0g and should be administered \u22652\u00a0h before or after SZC. The PK profile of cyclosporin was not affected by SZC co-administration.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ckj\/sfac205","type":"journal-article","created":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T22:23:31Z","timestamp":1663107811000},"page":"151-158","source":"Crossref","is-referenced-by-count":4,"title":["A Phase 1, open-label, crossover study evaluating the effect of a single dose of sodium zirconium cyclosilicate on the pharmacokinetics of tacrolimus and cyclosporin"],"prefix":"10.1093","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9643-1638","authenticated-orcid":false,"given":"Mats","family":"N\u00e5g\u00e5rd","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences , Research and Development, AstraZeneca, Gaithersburg, MD , 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