{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T19:40:46Z","timestamp":1778701246055,"version":"3.51.4"},"reference-count":38,"publisher":"Walter de Gruyter GmbH","issue":"5","funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_cclm-2020-1542_abs_001\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Therapeutic drug monitoring (TDM) plays a crucial role in personalized medicine. It helps clinicians to tailor drug dosage for optimized therapy through understanding the underlying complex pharmacokinetics and pharmacodynamics. Conventional, non-continuous TDM fails to provide real-time information, which is particularly important for the initial phase of immunosuppressant therapy, e.g., with cyclosporine (CsA) and mycophenolic acid (MPA).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2020-1542_abs_002\">\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We analyzed the time course over 8\u00a0h of total and free of immunosuppressive drug (CsA and MPA) concentrations measured by liquid chromatography-tandem mass spectrometry (LC-MS\/MS) in 16 kidney transplant patients. Besides repeated blood sampling, intravenous microdialysis was used for continuous sampling. Free drug concentrations were determined from ultracentrifuged EDTA-plasma (UC) and compared with the drug concentrations in the respective microdialysate (\u00b5D). \u00b5Ds were additionally analyzed for free CsA using a novel immunosensor chip integrated into a fluorescence detection platform. The potential of microdialysis coupled with an optical immunosensor for the TDM of immunosuppressants was assessed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2020-1542_abs_003\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Using LC-MS\/MS, the free concentrations of CsA (<jats:italic>f<\/jats:italic>CsA) and MPA (<jats:italic>f<\/jats:italic>MPA) were detectable and the time courses of total and free CsA comparable. <jats:italic>f<\/jats:italic>CsA and <jats:italic>f<\/jats:italic>MPA and area-under-the-curves (AUCs) in \u00b5Ds correlated well with those determined in UCs (r\u22650.79 and r\u22650.88, respectively). Moreover, <jats:italic>f<\/jats:italic>CsA in \u00b5Ds measured with the immunosensor correlated clearly with those determined by LC-MS\/MS (r=0.82).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2020-1542_abs_004\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The new microdialysis-supported immunosensor allows real-time analysis of immunosuppressants and tailor-made dosing according to the AUC concept. It readily lends itself to future applications as minimally invasive and continuous near-patient TDM.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/cclm-2020-1542","type":"journal-article","created":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T15:03:06Z","timestamp":1608649386000},"page":"935-945","source":"Crossref","is-referenced-by-count":10,"title":["Immunosuppressant quantification in intravenous microdialysate\u00a0\u2013 towards novel quasi-continuous therapeutic drug monitoring in transplanted patients"],"prefix":"10.1515","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7209-8842","authenticated-orcid":false,"given":"Susanne","family":"Weber","sequence":"first","affiliation":[{"name":"Institute of Clinical Chemistry and Pathobiochemistry , Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen , Munich , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Tombelli","sequence":"additional","affiliation":[{"name":"Institute of Applied Physics \u201cNello Carrara\u201d, National Research Council , Sesto Fiorentino (FI) , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ambra","family":"Giannetti","sequence":"additional","affiliation":[{"name":"Institute of Applied Physics \u201cNello Carrara\u201d, National Research Council , Sesto Fiorentino (FI) , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cosimo","family":"Trono","sequence":"additional","affiliation":[{"name":"Institute of Applied Physics \u201cNello Carrara\u201d, National Research Council , Sesto Fiorentino (FI) , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"O\u2019Connell","sequence":"additional","affiliation":[{"name":"Cornel Medical Ltd. , London , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Nephrology , Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen , Munich , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana B.","family":"Descalzo","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry , Universidad Complutense de Madrid , Madrid , Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heike","family":"Bittersohl","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Pathobiochemistry , Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen , Munich , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1228-0770","authenticated-orcid":false,"given":"Andreas","family":"Bietenbeck","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Pathobiochemistry , Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen , Munich , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Marquet","sequence":"additional","affiliation":[{"name":"U1248 IPPRITT, INSERM, University of Limoges , Limoges, CHU Limoges , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lutz","family":"Renders","sequence":"additional","affiliation":[{"name":"Department of Nephrology , Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen , Munich , Germany"},{"name":"German Centre for Infection Research (DZIF) , Munich , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillermo","family":"Orellana","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry , Universidad Complutense de Madrid , Madrid , Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Baldini","sequence":"additional","affiliation":[{"name":"Institute of Applied Physics \u201cNello Carrara\u201d, National Research Council , Sesto Fiorentino (FI) , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter B.","family":"Luppa","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Pathobiochemistry , Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen , Munich , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2020,12,15]]},"reference":[{"key":"2023033113430152511_j_cclm-2020-1542_ref_001","doi-asserted-by":"crossref","unstructured":"Freudenberger, K, Hilbig, U, Gauglitz, G. 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