{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:34:23Z","timestamp":1790786063368,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,8,22]],"date-time":"2016-08-22T00:00:00Z","timestamp":1471824000000},"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":[[2016,12]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>The combination of hydrocortisone and fludrocortisone improved outcomes in septic shock. However, the specific role of fludrocortisone remains controversial and its pharmacokinetics (PK) has never been investigated in septic shock. This study aimed at characterizing the PK of fludrocortisone in septic shock.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a single\u2010centre ancillary PK study of a large multinational trial of crystalloids versus colloids for acute hypovolemia in intensive care unit (ICU) patients. In 21 adults with septic shock, fludrocortisone plasma concentrations were measured by liquid chromatography\u2013mass spectrometry tandem analysis, before and repeatedly until 18\u00a0h after an oral dose of 50\u00a0\u03bcg. PK parameters were estimated using a nonlinear mixed\u2010effects modelling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Undetectable plasma concentrations were observed in 7 out of 21 patients. In the remaining 14 patients, plasma fludrocortisone concentrations were best described by a one\u2010compartmental model with first\u2010order absorption, a lag time (T<jats:sub>lag<\/jats:sub>) before the absorption phase, and first\u2010order elimination. Severity of illness, as quantified by Simplified Acute Physiology Score II, significantly increased T<jats:sub>lag<\/jats:sub> and apparent clearance. There was a large inter\u2010individual variability in PK parameters. The population estimates of PK parameters (inter\u2010individual variability) were: T<jats:sub>lag<\/jats:sub> 0.65\u00a0h (98%), apparent clearance 40\u00a0l\u00a0h<jats:sup>\u22121<\/jats:sup> (49%) and apparent volume of distribution 78\u00a0l (75%). Plasma half\u2010life was estimated at 1.35\u00a0h (95% CI, 0.84\u20132.03) and area under the curve of plasma concentrations was estimated at 1.25\u00a0\u03bcg\u00a0h\u00a0l<jats:sup>\u22121<\/jats:sup> (95% CI, 1.09\u20131.46).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A single oral dose of fludrocortisone yielded undetectable plasma concentrations in one\u2010third of adults with septic shock. Fludrocortisone PK showed a short plasma elimination half\u2010life and a large inter\u2010individual variability.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13065","type":"journal-article","created":{"date-parts":[[2016,7,15]],"date-time":"2016-07-15T12:20:50Z","timestamp":1468585250000},"page":"1509-1516","source":"Crossref","is-referenced-by-count":38,"title":["Pharmacokinetics of oral fludrocortisone in septic shock"],"prefix":"10.1111","volume":"82","author":[{"given":"Andrea","family":"Polito","sequence":"first","affiliation":[{"name":"Department of Intensive Care Raymond Poincar\u00e9 Hospital (AP\u2010HP)  Garches France"},{"name":"Laboratory of Cell Death, Inflammation and Infection INSERM UMR 1173 University of Versailles Saint\u2010Quentin\u2010en\u2010Yvelines  Garches France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noureddine","family":"Hamitouche","sequence":"additional","affiliation":[{"name":"INSERM 1414 Clinical Investigation Centre  Rennes 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