{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T04:04:18Z","timestamp":1792728258949,"version":"4.5.0"},"reference-count":52,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,12,13]],"date-time":"2020-12-13T00:00:00Z","timestamp":1607817600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>To determine the distribution of vancomycin into the cerebrospinal fluid (CSF) in patients with external ventricular drain (EVD)\u2010associated ventriculitis, the pharmacokinetics of vancomycin were evaluated and covariate relationships explored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>For the population pharmacokinetic model patients were recruited in a neurocritical care unit at the University Hospital of Muenster in the period between January 2014 and June 2015. All patients had a clinical evidence of EVD\u2010associated ventriculitis. Population pharmacokinetic analysis of vancomycin was performed using NONMEM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 184 blood and 133 CSF samples were collected from 29 patients. The final population pharmacokinetic model is a three\u2010compartment model with linear elimination. Creatinine clearance (Cl<jats:sub>Cr<\/jats:sub>) and CSF\u2010lactate were detected as significant covariates, showing that the total vancomycin plasma clearance (Cl) depends on Cl<jats:sub>Cr<\/jats:sub>and furthermore the clearance (Cl<jats:sub>dif<\/jats:sub>) between the central and CSF compartment correlates with CSF lactate concentration. Based on the final model, the following values were estimated by NONMEM: Cl\u00a0=\u00a05.15\u00a0L\/h,<jats:italic>Q<\/jats:italic>(intercompartmental clearance)\u00a0=\u00a03.31\u00a0L\/h, Cl<jats:sub>dif<\/jats:sub>\u00a0=\u00a00.0031\u00a0L\/h,<jats:italic>V<\/jats:italic><jats:sub>central<\/jats:sub>\u00a0=\u00a042.1\u00a0L,<jats:italic>V<\/jats:italic><jats:sub>CSF<\/jats:sub>\u00a0=\u00a00.32\u00a0L and the value of<jats:italic>V<\/jats:italic><jats:sub>peripheral<\/jats:sub>was fixed to 86.2\u00a0L. With the developed pharmacokinetic model, area under the curve (AUC) values as well as CSF trough levels were simulated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Based on our analysis, the dosing of vancomycin should be referred to the degree of inflammation (derived from the CSF lactate concentration) and renal function (derived from Cl<jats:sub>Cr<\/jats:sub>).<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14657","type":"journal-article","created":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T19:25:58Z","timestamp":1605641158000},"page":"2502-2510","source":"Crossref","is-referenced-by-count":24,"title":["Population pharmacokinetics of vancomycin in patients with external ventricular drain\u2010associated ventriculitis"],"prefix":"10.1111","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7715-089X","authenticated-orcid":false,"given":"Kris Oliver","family":"Jalusic","sequence":"first","affiliation":[{"name":"Department of 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