{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:34:56Z","timestamp":1791480896582,"version":"4.3.4"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T00:00:00Z","timestamp":1723680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"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 goal of the study was to describe the population pharmacokinetics of trimethoprim, sulfamethoxazole, and <jats:italic>N<\/jats:italic>\u2010acetyl sulfamethoxazole in hospitalized patients. Furthermore, this study used the model to optimize dosing regimens of cotrimoxazole for <jats:italic>Pneumocystis jirovecii<\/jats:italic> pneumonia and in patients with renal insufficiency or with continuous renal replacement therapy (CRRT). This was a retrospective multicenter observational cohort study based on therapeutic drug monitoring (TDM) data from hospitalized patients treated with cotrimoxazole. We developed two population pharmacokinetic (POPPK) models: a model of trimethoprim and an integrated model with both sulfamethoxazole and <jats:italic>N<\/jats:italic>\u2010acetyl sulfamethoxazole concentrations. Monte Carlo simulations were performed to determine the optimal dosing regimen. A total of 348 measurements from 168 patients were available. The estimated glomerular filtration rate (eGFR) and CRRT were included as covariates on the clearance of all three compounds. Cotrimoxazole TID 1,920\u2009mg and b.i.d. 2,400\u2009mg led to sufficient exposure for infections with <jats:italic>P. jirovecii<\/jats:italic> in patients without renal insufficiency. To reach equivalent exposure, a dose reduction of 33.3% is needed in patients with an eGFR of 10\u2009mL\/minute\/1.73\u2009m<jats:sup>2<\/jats:sup> and of 16.7% for an eGFR of 30\u2009mL\/minute\/1.73\u2009m<jats:sup>2<\/jats:sup>. <jats:italic>N<\/jats:italic>\u2010acetyl sulfamethoxazole accumulates in patients with a reduced eGFR. CRRT increased the clearance of sulfamethoxazole, but not trimethoprim or <jats:italic>N<\/jats:italic>\u2010acetyl sulfamethoxazole, compared with the median clearance in the population. Doubling the sulfamethoxazole dose is needed for patients on CRRT to reach equivalent exposure.<\/jats:p>","DOI":"10.1002\/cpt.3421","type":"journal-article","created":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T06:35:16Z","timestamp":1723790116000},"page":"184-192","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Population Pharmacokinetics of Trimethoprim\/Sulfamethoxazole: Dosage Optimization for Patients with Renal Insufficiency or Receiving Continuous Renal Replacement Therapy"],"prefix":"10.1002","volume":"117","author":[{"given":"Emiel","family":"Leegwater","sequence":"first","affiliation":[{"name":"Department of Hospital Pharmacy Haga Teaching Hospital  The Hague The Netherlands"},{"name":"Apotheek Haagse Ziekenhuizen  The Hague The\u00a0Netherlands"},{"name":"Department of Infectious Diseases Leiden University Center for Infectious Diseases (LU\u2010CID) Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Baidjoe","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy Erasmus University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7116-7794","authenticated-orcid":false,"given":"Erik B.","family":"Wilms","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy Haga Teaching Hospital  The Hague The Netherlands"},{"name":"Apotheek Haagse Ziekenhuizen  The Hague The\u00a0Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo G.","family":"Visser","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Leiden University Center for Infectious Diseases (LU\u2010CID) Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1429-4789","authenticated-orcid":false,"given":"Daniel J.","family":"Touw","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4452-8443","authenticated-orcid":false,"given":"Brenda C. M.","family":"de Winter","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy Erasmus University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark G. J.","family":"de Boer","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Leiden University Center for Infectious Diseases (LU\u2010CID) Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4847-4948","authenticated-orcid":false,"given":"Judith","family":"van Paassen","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte H. S. B.","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Department of Intensive Care University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4544-4807","authenticated-orcid":false,"given":"Joffrey","family":"van Prehn","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology Leiden University Center for Infectious Diseases (LU\u2010CID) Leiden University Medical Center  Leiden The\u00a0Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5980-6947","authenticated-orcid":false,"given":"Teun","family":"van Gelder","sequence":"additional","affiliation":[{"name":"Department Clinical Pharmacy and Toxicology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3219-253X","authenticated-orcid":false,"given":"Dirk Jan A. 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