{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T23:56:44Z","timestamp":1771545404395,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,4,2]],"date-time":"2018-04-02T00:00:00Z","timestamp":1522627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Previously, we have reported an association between clozapine use and elevated FL3 neutrophil fluorescence, a flow\u2010cytometric parameter for cell viability. Here, we developed and evaluated a pharmacokinetic\u2013pharmacodynamic model relating FL3\u2010fluorescence to clozapine exposure and derived a nomogram for estimation of long\u2010term adherence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data from 27 patients initiating clozapine were analysed using nonlinear mixed effects modelling. A previously described pharmacokinetic model for clozapine was coupled to a FL3 fluorescence model. For this, an effect compartment with clozapine concentrations as input and a first order decay rate as output was linked with an E<jats:sub>max<\/jats:sub> model to FL3\u2010fluorescence. FL3\u2010fluorescence was simulated for clozapine doses of 50, 150 and 400\u00a0mg daily (<jats:italic>n<\/jats:italic>\u00a0=\u00a010 000) to establish the nomogram. Finally, true simulated adherence (% of daily doses taken over 100\u00a0days) was compared to nomogram\u2010estimated adherence to evaluate the performance of the nomogram.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The half\u2010life of FL3\u2010fluorescence was estimated at 228\u00a0h (coefficient of variation 35%). Median absolute prediction errors of the nomogram in case of fully random adherence for 50, 150 and 400\u00a0mg ranged from \u20130.193% to \u20130.525%. The nomogram performed slightly worse in case of nonrandom adherence (median prediction error up to 5.19%), but was still clinically acceptable. Compliance patterns containing longer drug holidays revealed that the nomogram adequately estimates compliance over approximately the last 3\u00a0weeks prior to FL3\u2010measurement.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our nomogram could provide information regarding long\u2010term adherence based on prescribed clozapine dose and FL3\u2010fluorescence. Future studies should further explore the clinical value of this biomarker and nomogram.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13546","type":"journal-article","created":{"date-parts":[[2018,2,10]],"date-time":"2018-02-10T03:02:41Z","timestamp":1518231761000},"page":"1228-1237","source":"Crossref","is-referenced-by-count":5,"title":["Development of a nomogram for the estimation of long\u2010term adherence to clozapine therapy using neutrophil fluorescence"],"prefix":"10.1111","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8471-6409","authenticated-orcid":false,"given":"W. H.","family":"Man","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy University Medical Center Utrecht  The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"P\u00e9rez\u2010Pitarch","sequence":"additional","affiliation":[{"name":"Pharmacy Department University Clinical Hospital of Valencia  Spain"},{"name":"Department of Pharmacy and Pharmaceutical Technology University of Valencia  Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I.","family":"Wilting","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy University Medical Center Utrecht  The Netherlands"},{"name":"Division of Pharmacoepidemiology and Clinical Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science Utrecht University  The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. R.","family":"Heerdink","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy University Medical Center Utrecht  The Netherlands"},{"name":"Division of Pharmacoepidemiology and Clinical Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science Utrecht University  The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. W.","family":"van Solinge","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Haematology University Medical Center Utrecht  The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. C. G.","family":"Egberts","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy University Medical Center Utrecht  The Netherlands"},{"name":"Division of Pharmacoepidemiology and Clinical Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science Utrecht University  The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. D. R.","family":"Huitema","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy University Medical Center Utrecht  The Netherlands"},{"name":"Department of Pharmacy &amp; Pharmacology Netherlands Cancer Institute  The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,4,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(99)00153-5"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.158.4.518"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1988.01800330013001"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1992.01820050009001"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1176\/ps.49.8.1029"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002826-199518003-00003"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v64n1105"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v63n1007"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1176\/ps.49.2.196"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0030-1254090"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ps.55.8.886"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2012.05.001"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005650-200208000-00002"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.108.051979"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002130050028"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3109\/13651500903434453"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.forsciint.2004.10.024"},{"issue":"108","key":"e_1_2_10_19_1","article-title":"Neutrophil fluorescence in patients using clozapine [abstract]","volume":"25","author":"Hoffmann J","year":"2000","journal-title":"Ned Tijdschr Klin Chem"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2013.08.005"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1515\/CCLM.2007.009"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/509513"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-553X.2007.00981.x"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1532\/LH96.05041"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1532\/LH96.04017"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2013.24"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e31819c7037"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2012.04167.x"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1121"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(99)00176-3"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0740-5472(93)90006-N"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2007.03068.x"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-015-0814-z"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbcp.13546","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.13546","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T06:42:42Z","timestamp":1695019362000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.13546"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,2]]},"references-count":32,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,6]]}},"alternative-id":["10.1111\/bcp.13546"],"URL":"https:\/\/doi.org\/10.1111\/bcp.13546","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,2]]}}}