{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T11:14:21Z","timestamp":1768475661703,"version":"3.49.0"},"reference-count":84,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T00:00:00Z","timestamp":1656460800000},"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":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cystic fibrosis (CF) has been linked to altered drug disposition in various studies. However, the magnitude of these changes, influencing factors, and underlying mechanisms remain a matter of debate. The primary aim of this work was therefore to quantify changes in drug disposition (top\u2010down) and the pathophysiological parameters known to affect pharmacokinetics (PKs; bottom\u2010up). This was done through meta\u2010analyses and meta\u2010regressions in addition to theoretical PK simulations. Volumes of distribution and clearances were found to be elevated in people living with CF. These increases were larger in studies which included patients with pulmonary exacerbations. Differences in clearance were smaller in more recent studies and when results were normalized to body surface area or lean body mass instead of body weight. For the physiological parameters investigated, measured glomerular filtration rate and serum cytokine concentrations were found to be elevated in people living with CF, whereas serum albumin and creatinine levels were decreased. Possible pathophysiological mechanisms for these alterations relate to renal hyperfiltration, increases in free fraction, and inflammation. No differences were detected for cardiac output, body fat, fat free mass, hematocrit, creatinine clearance, and the activity of drug metabolizing enzymes. These findings imply that, in general, lower total plasma concentrations of drugs can be expected in people living with CF, especially when pulmonary exacerbations are present. Given the potential effect of CF on plasma protein binding and the variability in outcome observed between studies, the clinical relevance of adapting existing dosage regimens should be evaluated on a case\u2010by\u2010case basis.<\/jats:p>","DOI":"10.1002\/psp4.12832","type":"journal-article","created":{"date-parts":[[2022,6,24]],"date-time":"2022-06-24T07:10:41Z","timestamp":1656054641000},"page":"951-966","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Altered intravenous drug disposition in people living with cystic fibrosis: A meta\u2010analysis integrating top\u2010down and bottom\u2010up data"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3858-8017","authenticated-orcid":false,"given":"Pieter\u2010Jan","family":"De Sutter","sequence":"first","affiliation":[{"name":"Department of Bioanalysis, Laboratory of Medical Biochemistry and Clinical Analysis, Faculty of Pharmaceutical Sciences Ghent University  Ghent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7938-1675","authenticated-orcid":false,"given":"Maxime","family":"Van Haeverbeke","sequence":"additional","affiliation":[{"name":"Department of Data Analysis and Mathematical Modelling, KERMIT Research Unit Ghent University  Ghent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7242-0747","authenticated-orcid":false,"given":"Eva","family":"Van Braeckel","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Ghent University Hospital  Ghent Belgium"},{"name":"Department of Internal Medicine and Paediatrics, Faculty of Medicine and Health Sciences Ghent University  Ghent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5609-3726","authenticated-orcid":false,"given":"Stephanie","family":"Van Biervliet","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Paediatrics, Faculty of Medicine and Health Sciences Ghent University  Ghent Belgium"},{"name":"Department of Paediatric Gastroenterology, Hepatology and Nutrition Ghent University Hospital  Ghent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4505-5510","authenticated-orcid":false,"given":"Jan","family":"Van Bocxlaer","sequence":"additional","affiliation":[{"name":"Department of Bioanalysis, Laboratory of Medical Biochemistry and Clinical Analysis, Faculty of Pharmaceutical Sciences Ghent University  Ghent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3094-7110","authenticated-orcid":false,"given":"An","family":"Vermeulen","sequence":"additional","affiliation":[{"name":"Department of Bioanalysis, Laboratory of Medical Biochemistry and Clinical Analysis, Faculty of Pharmaceutical Sciences Ghent University  Ghent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0503-3560","authenticated-orcid":false,"given":"Elke","family":"Gasthuys","sequence":"additional","affiliation":[{"name":"Department of Bioanalysis, Laboratory of Medical Biochemistry and Clinical Analysis, Faculty of Pharmaceutical Sciences Ghent University  Ghent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,6,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)12567-6"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI5731"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.4187\/respcare.06697"},{"key":"e_1_2_8_5_1","first-page":"9","article-title":"A millennial view of cystic fibrosis","volume":"19","author":"Dodge JA","year":"2015","journal-title":"Dev Period Med"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCP.0b013e3283659ef2"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30255"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1843.2010.01771.x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2017.11.019"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201606-1250PP"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2019.10.025"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.23505"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-020-00932-9"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008634911114"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199835040-00004"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-018-0678-x"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2288-8-32"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00203"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2288-14-135"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/096228029300200202"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3102\/10769986030003261"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1482"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0006-341X.2000.00455.x"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2018.02.021"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.2165\/11318160-000000000-00000"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1136\/ebmental-2019-300117"},{"key":"e_1_2_8_27_1","unstructured":"HarrerM CuijpersP FurukawaT EbertDD.dmetar: Companion R Package For The Guide \u201cDoing Meta\u2010Analysis in R\u201d [Internet];2019.http:\/\/dmetar.protectlab.org\/"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/1179548419835788"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.729"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/59.1.123"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101436"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/MAJ.0000000000000592"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes11121509"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01522-06"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1994.66"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1993.154"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1992.tb04096.x"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1991.47"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1984.187"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(84)80317-0"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1983.tb09715.x"},{"key":"e_1_2_8_42_1","first-page":"1038","article-title":"Enhanced renal excretion of Dicloxacillin in patients with cystic fibrosis","volume":"56","author":"Jusko WJ","year":"1975","journal-title":"Pediatrics"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.2001.01370.x"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0773.1996.tb00211.x"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1995.tb04415.x"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002280050578"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(79)80394-7"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2021.1836157"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics11060286"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1097\/MBC.0b013e3283249ac6"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-020-00970-3"},{"key":"e_1_2_8_52_1","unstructured":"ZolinA OrentiA NaehrlichL JungA vanRensJ.ECFS Annual Report 2018 [Internet];2020 p.1\u2013173.https:\/\/www.ecfs.eu\/sites\/default\/files\/general\u2010content\u2010files\/working\u2010groups\/ecfs\u2010patient\u2010registry\/ECFSPR_Report_2018_v1.4.pdf"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2007.10.003"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2019.01.002"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-2135"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01956149"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2017.08.011"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.59.4.588"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.2165\/11598930-000000000-00000"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2016.07.011"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.00750209"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-018-0636-7"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2018.06.002"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2009.12.002"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2008.07.004"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(05)80149-0"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.5114\/pg.2014.43574"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30148"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfda.2018.11.005"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00192559"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1023"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000003312"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-013-0036-y"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14326"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(19)30337-6"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202008-3176LE"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(15)00545-7"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-015-3834-2"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCP.0000000000000423"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.24917"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2003.10.005"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1994.173"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1875-9114.1996.tb02992.x"},{"key":"e_1_2_8_84_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1991.209"},{"key":"e_1_2_8_85_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1988.177"}],"container-title":["CPT: Pharmacometrics &amp; Systems Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.12832","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/psp4.12832","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.12832","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,30]],"date-time":"2023-12-30T04:20:00Z","timestamp":1703910000000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/psp4.12832"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,29]]},"references-count":84,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["10.1002\/psp4.12832"],"URL":"https:\/\/doi.org\/10.1002\/psp4.12832","archive":["Portico"],"relation":{},"ISSN":["2163-8306","2163-8306"],"issn-type":[{"value":"2163-8306","type":"print"},{"value":"2163-8306","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,29]]},"assertion":[{"value":"2022-02-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}