{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:59:34Z","timestamp":1783490374235,"version":"3.55.0"},"reference-count":22,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,5,2]],"date-time":"2023-05-02T00:00:00Z","timestamp":1682985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Fibrinogen is the key substrate for coagulation. Fibrinogen pharmacokinetics (PK) after single doses of fibrinogen concentrate (FC), using modelling approaches, has only been evaluated in congenital afibrinogenaemic patients. The aims of this study are to characterize the fibrinogen PK in patients with acquired\u2014chronic (cirrhosis) or acute\u2014hypofibrinogenaemia (critical haemorrhage), showing endogenous production. Influencing factors of differences on the fibrinogen PK between subpopulations will be identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 428 time\u2013concentration values from 132 patients were recorded. Eighty\u2010two out of 428 values were from 41 cirrhotic patients administered with placebo and 90 out of 428 were from 45 cirrhotic patients that were given FC, 161 out of 428 values were from 14 afibrinogenaemic patients and 95 out of 428 values were from 32 severe acute trauma haemorrhagic patients. A turnover model that accounted for endogenous production and exogenous dose was fitted using NONMEM74. The production rate (Ksyn), distribution volume (V), plasma clearance (CL) and concentration yielding to 50% of maximal fibrinogen production (<jats:italic>EC<\/jats:italic>50) were estimated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fibrinogen disposition was described by a one\u2010compartment model with CL and V values of 0.0456\u2009L\u00b7h<jats:sup>\u22121<\/jats:sup> and 4.34\u2009L\u00b770\u2009kg<jats:sup>\u22121<\/jats:sup>, respectively. Body weight was statistically significant in V. Three different Ksyn values were identified that increased from 0.00439\u2009g\u00b7h<jats:sup>\u22121<\/jats:sup> (afibrinogenaemia), to 0.0768\u2009g\u00b7h<jats:sup>\u22121<\/jats:sup> (cirrhotics) and 0.1160\u2009g\u00b7h<jats:sup>\u22121<\/jats:sup> (acute severe trauma). <jats:italic>EC<\/jats:italic>50 was of 0.460\u2009g\u00b7L<jats:sup>\u22121<\/jats:sup>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This model will be key as a support tool for dose calculation to achieve specified target fibrinogen concentrations, in each of the studied populations.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15741","type":"journal-article","created":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T23:01:36Z","timestamp":1681254096000},"page":"2703-2713","source":"Crossref","is-referenced-by-count":2,"title":["Population pharmacokinetic modelling of fibrinogen in patients with congenital or acquired\u2014chronic or acute\u2014hypofibrinogenaemia"],"prefix":"10.1111","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7259-0199","authenticated-orcid":false,"given":"Helena","family":"Colom","sequence":"first","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology and Physical\u2010Chemistry, Faculty of Pharmacy and Food Sciences University of Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annabel","family":"Blasi","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology Hospital Clinic, IDIBAPS, University of Barcelona Health Campus  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Montoro","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy Vall d'Hebron University Hospital  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel\u2010Guillermo","family":"Ar\u00e9valo","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy Vall d'Hebron University Hospital  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep Maria","family":"Cendr\u00f3s","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology and Physical\u2010Chemistry, Faculty of Pharmacy and Food Sciences University of Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoni","family":"Sabat\u00e9","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology Hospital Universitari de Bellvitge, IDIBELL, University of Barcelona Health Campus  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,2]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100028\u20101091330"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000539-199508000-00026"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/MBC.0b013e32830f1b68"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100038\u20101666861"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538\u20107836.2008.03076.x"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538\u20107836.2009.03633.x"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14147"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13752"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/vox.12598"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054\u2010015\u20100817\u20109"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/MBC.0000000000000543"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000205234"},{"key":"e_1_2_12_14_1","volume-title":"NONMEM User's Guide","author":"Bauer R","year":"2011"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-2607(98)00067-4"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2005.04.005"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1012299115260"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.24.25"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01117450"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248\u2010009\u20109133\u20100"},{"key":"e_1_2_12_21_1","unstructured":"HolfordN.The visual predictive check\u2014superiority to standard diagnostic (Rorschach) plots. 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