{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:44:26Z","timestamp":1747183466439,"version":"3.40.5"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:00:00Z","timestamp":1663718400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["848016010"],"award-info":[{"award-number":["848016010"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>Pemetrexed is a cytotoxic drug used for the treatment of lung cancer and mesothelioma. The use of a low test dosing of cytotoxic drugs may aid in dose individualization without causing harm. The aim of this proof\u2010of\u2010concept study was to assess if the pharmacokinetics (PKs) of a test dose could predict the PKs of a therapeutic pemetrexed dose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Ten patients received both a low test dose (100\u2009\u03bcg) and a therapeutic dose of pemetrexed after which plasma concentrations pemetrexed were measured. PK analysis was performed by means of nonlinear mixed\u2010effects modelling. The predictive performances of test dose clearance and renal function towards a therapeutic dose were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The PKs of a pemetrexed test dose were best described by a one\u2010compartment model with linear elimination. A high variability in the administered dose was observed for the test dose, but not for the therapeutic dose. A statistically significant correlation between test dose clearance and therapeutic dose clearance was observed (Spearman's rho: 0.758, <jats:italic>P<\/jats:italic>\u00a0=\u20090.02). The predictive performance of test dose clearance was worse than renal function: mean predictive error (+95% confidence interval [CI]) 53.9% (50.1\u201057.6%) <jats:italic>vs<\/jats:italic> 19.4% (12.4\u201026.4%) and normalized root\u2010mean square error (+95% CI) 57.8% (30.5\u201085.1%) <jats:italic>vs<\/jats:italic> 25.7% (20.3\u201031.0%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We show that test dosing of pemetrexed is feasible, but there seems no added value for a low test dosing in the dose individualization of pemetrexed.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15520","type":"journal-article","created":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T14:49:23Z","timestamp":1662130163000},"page":"699-704","source":"Crossref","is-referenced-by-count":1,"title":["Prediction of the pharmacokinetics of pemetrexed with a low test dose: A proof\u2010of\u2010concept study"],"prefix":"10.1111","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6399-2604","authenticated-orcid":false,"given":"Ren\u00e9 J.","family":"Boosman","sequence":"first","affiliation":[{"name":"Department of Pharmacy &amp; Pharmacology Antoni van Leeuwenhoek \u2013 The Netherlands Cancer Institute  Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1991-0552","authenticated-orcid":false,"given":"Nikki","family":"de Rouw","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Radboud Institute for Health Sciences Radboud University Medical Center  Nijmegen the Netherlands"},{"name":"Department of Pharmacy Jeroen Bosch Hospital  \u2018s\u2010Hertogenbosch the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alwin D. 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