{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T05:42:13Z","timestamp":1784612533334,"version":"3.55.0"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","funder":[{"name":"Minist\u00c3\u00a8re de l\u00e2\u20acEnseignement Sup\u00c3\u00a9rieur et de la Recherche Scientifique"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Tacrolimus is the most frequently used immunosuppressive drug for preventing renal rejection. However, its use is hampered by its narrow therapeutic index and large intra and interpatient variability in pharmacokinetics. The objective of this study was to externally validate a tacrolimus population pharmacokinetic model developed for the Dutch population and adjust the model for the Tunisian population for use in predicting the starting dose requirement after kidney transplantation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>Data on tacrolimus exposure were obtained from kidney transplant recipients (KTRs) during the first 3 months post-transplantation. External validation of the Dutch model and its adjustment for the Tunisian population was performed using nonlinear mixed-effects modeling.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>In total, 1901 whole-blood predose tacrolimus concentrations from 196 adult KTRs were analyzed. According to a visual predictive check, the Dutch model underestimated the starting dose for the Tunisian adult population. The effects of age, together with the <jats:italic toggle=\"yes\">CYP3A5*3<\/jats:italic> and <jats:italic toggle=\"yes\">CYP3A4*22<\/jats:italic> genotypes on tacrolimus clearance were significantly different in the Tunisian population than in the Dutch population. Based on a bodyweight-based dosing, only 21.9% of tacrolimus concentrations were within the target range, whereas this was estimated to be 54.0% with the newly developed model-based dosing. After adjustment, the model was successfully validated internally in a Tunisian population.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>A starting-dose population pharmacokinetic model of tacrolimus for Tunisian KTRs was developed based on a previously published Dutch model. Using this starting dose could potentially increase the percentage of patients achieving target tacrolimus concentrations after the initial starting dose.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/ftd.0000000000001147","type":"journal-article","created":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T13:06:29Z","timestamp":1701263189000},"page":"57-66","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":6,"title":["A Population Pharmacokinetic Model to Predict the Individual Starting Dose of Tacrolimus for Tunisian Adults after Renal Transplantation"],"prefix":"10.1097","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5609-4611","authenticated-orcid":false,"given":"Amani","family":"Abderahmene","sequence":"first","affiliation":[{"name":"Department of Biochemistry,LR12SP11, Sahloul University Hospital, Sousse, University of Monastir Faculty of Pharmacy of Monastir, Monastir, Tunisia;"},{"name":"Rotterdam Clinical Pharmacometrics Group, Rotterdam, the Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marith I.","family":"Francke","sequence":"additional","affiliation":[{"name":"Rotterdam Clinical Pharmacometrics Group, Rotterdam, the Netherlands;"},{"name":"Division of Nephrology and Transplantation, Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, the Netherlands;"},{"name":"Erasmus MC Transplant Institute, Rotterdam, the Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise M.","family":"Andrews","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy, Meander MC, Amersfoort, the Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis A.","family":"Hesselink","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Transplantation, Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, the Netherlands;"},{"name":"Erasmus MC Transplant Institute, Rotterdam, the Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorra","family":"Amor","sequence":"additional","affiliation":[{"name":"Department of Biochemistry,LR12SP11, Sahloul University Hospital, Sousse, University of Monastir Faculty of Pharmacy of Monastir, Monastir, Tunisia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wissal","family":"Sahtout","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Sahloul University Hospital, Sousse, Tunisia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa","family":"Ajmi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry,LR12SP11, Sahloul University Hospital, Sousse, University of Monastir Faculty of Pharmacy of Monastir, Monastir, Tunisia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayfa","family":"Mastouri","sequence":"additional","affiliation":[{"name":"Department of Biochemistry,LR12SP11, Sahloul University Hospital, Sousse, University of Monastir Faculty of Pharmacy of Monastir, Monastir, Tunisia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Bouslama","sequence":"additional","affiliation":[{"name":"Department of Biochemistry,LR12SP11, Sahloul University Hospital, Sousse, University of Monastir Faculty of Pharmacy of Monastir, Monastir, Tunisia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorsaf","family":"Zellama","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Sahloul University Hospital, Sousse, Tunisia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma","family":"Omezzine","sequence":"additional","affiliation":[{"name":"Department of Biochemistry,LR12SP11, Sahloul University Hospital, Sousse, University of Monastir Faculty of Pharmacy of Monastir, Monastir, Tunisia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda C. 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