{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T21:27:50Z","timestamp":1781645270420,"version":"3.54.5"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T00:00:00Z","timestamp":1723593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>The intracellular tacrolimus concentration in CD3<jats:sup>+<\/jats:sup> T lymphocytes is proposed to be a better representative of the active component of tacrolimus than the whole blood concentration. However, intracellular measurements are complicated. Therefore, the aim of this study was to describe the relationship between intracellular and whole blood tacrolimus concentrations in a population pharmacokinetic model. Twenty\u2010eight <jats:italic>de novo<\/jats:italic> kidney transplant recipients, treated with a once\u2010daily oral extended\u2010release tacrolimus formulation, were followed during the first\u2010month post\u2010transplantation. Additional whole blood and intracellular tacrolimus concentrations were measured at day 6\u2009\u00b1\u20091 (pre\u2010dose, 4 and 8\u2009hours post\u2010dose) and day 14\u2009\u00b1\u20093 (pre\u2010dose) post\u2010transplantation. Pharmacokinetic analysis was performed using nonlinear mixed effects modeling software (NONMEM). The ratio between intracellular (<jats:italic>n<\/jats:italic>\u2009=\u2009109) and whole blood (<jats:italic>n<\/jats:italic>\u2009=\u2009248) concentrations was best described by a two\u2010compartment whole blood model with an additional intracellular compartment without mass transfer from the central compartment. The ratio remained stable over time. Prednisolone dose influenced the absorption rate of tacrolimus, while hemoglobin, <jats:italic>CYP3A4*22<\/jats:italic> allele carrier, and <jats:italic>CYP3A5<\/jats:italic> expresser status were associated with the oral clearance of tacrolimus (<jats:italic>P<\/jats:italic>\u2010value\u2009&lt;\u20090.001). Furthermore, the intracellular tacrolimus concentrations were correlated with the intracellular production of interleukin\u20102 (<jats:italic>P<\/jats:italic>\u2010value 0.015). The intracellular tacrolimus concentration can be predicted from a measured whole blood concentration using this model, without the need for repeated intracellular measurements. This knowledge is particularly important when the intracellular concentration is ready to be implemented into clinical practice, to overcome the complexities of cell isolation and analytical methods.<\/jats:p>","DOI":"10.1002\/cpt.3419","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T07:29:31Z","timestamp":1723620571000},"page":"162-173","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Prediction of the Intra\u2010T Lymphocyte Tacrolimus Concentration after Kidney Transplantation with Population Pharmacokinetic Modeling"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4087-9032","authenticated-orcid":false,"given":"Suwasin","family":"Udomkarnjananun","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Faculty of Medicine, Thai Red Cross Society Chulalongkorn University and King Chulalongkorn Memorial Hospital  Bangkok Thailand"},{"name":"Department of Internal Medicine, Erasmus MC Transplant Institute University Medical Center  Rotterdam The\u00a0Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8759-9866","authenticated-orcid":false,"given":"Maaike R.","family":"Schagen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Erasmus MC Transplant Institute University Medical Center  Rotterdam The\u00a0Netherlands"},{"name":"Rotterdam Clinical Pharmacometrics Group  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Volarevi\u0107","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy Erasmus MC, University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daan","family":"van de Velde","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy Erasmus MC, University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjolein","family":"Dieterich","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Erasmus MC Transplant Institute University Medical Center  Rotterdam The\u00a0Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Matic","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry Erasmus MC, University Medical Center  Rotterdam The\u00a0Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla C.","family":"Baan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Erasmus MC Transplant Institute University Medical Center  Rotterdam The\u00a0Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlies E. 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