{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:27:10Z","timestamp":1791041230643,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2017,3,31]],"date-time":"2017-03-31T00:00:00Z","timestamp":1490918400000},"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":[[2017,8]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Midazolam is the drug of choice for palliative sedation and is titrated to achieve the desired level of sedation. Because of large inter\u2010individual variability (IIV), however, the time it takes to achieve adequate sedation varies widely. It would therefore greatly improve clinical care if an individualized dose could be determined beforehand. To find clinically relevant parameters for dose individualization, we performed a pharmacokinetic study on midazolam, 1OH\u2010midazolam (1\u2010OH\u2010M) and 1OH\u2010midazolam\u2010glucuronide (1\u2010OH\u2010MG) in terminally ill patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using nonlinear mixed effects modelling (NONMEM 7.2), a population pharmacokinetic analysis was conducted with 192 samples from 45 terminally ill patients who received midazolam either orally or subcutaneously. The covariates analysed were patient characteristics, co\u2010medication and blood chemistry levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The data were accurately described by a one compartment model for midazolam, 1\u2010OH\u2010M and 1\u2010OH\u2010MG. The population mean estimates for midazolam, 1\u2010OH\u2010M and 1\u2010OH\u2010MG clearance were 8.4\u00a0l\u00a0h<jats:sup>\u22121<\/jats:sup> (RSE 9%, IIV 49%), 45.4\u00a0l\u00a0h<jats:sup>\u22121<\/jats:sup> (RSE 12%, IIV 60.5%) and 5.1\u00a0l\u00a0h<jats:sup>\u22121<\/jats:sup> (RSE 11%, IIV 49.9%), respectively. 1\u2010OH\u2010MG clearance was correlated with the estimated glomular filtration rate (eGFR) explaining 28.4% of the IIV in 1\u2010OH\u2010MG clearance. In addition, low albumin levels were associated with decreased midazolam clearance, explaining 18.2% of the IIV.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study indicates albumin levels and eGFR as relevant clinical parameters to optimize midazolam dosing in terminally ill patients. The correlation between low albumin levels and decreased midazolam clearance is probably a result of inflammatory response as high CRP levels were correlated in a similar way.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13259","type":"journal-article","created":{"date-parts":[[2017,2,8]],"date-time":"2017-02-08T13:02:46Z","timestamp":1486558966000},"page":"1701-1712","source":"Crossref","is-referenced-by-count":28,"title":["Hypoalbuminaemia and decreased midazolam clearance in terminally ill adult patients, an inflammatory effect?"],"prefix":"10.1111","volume":"83","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6436-9825","authenticated-orcid":false,"given":"Linda G.","family":"Franken","sequence":"first","affiliation":[{"name":"Department of Hospital Pharmacy Erasmus Medical Centre  Rotterdam Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anniek D.","family":"Masman","sequence":"additional","affiliation":[{"name":"Palliative Care Centre Laurens Cadenza  Rotterdam Netherlands"},{"name":"Intensive Care, Department of Paediatric Surgery Erasmus MC\u2010Sophia Children's Hospital  Rotterdam Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda C. 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