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Novel population pharmacokinetic approach to explain the differences between cystic fibrosis patients and healthy volunteers via protein binding

Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-196934
  • The pharmacokinetics in patients with cystic fibrosis (CF) has long been thought to differ considerably from that in healthy volunteers. For highly protein bound β-lactams, profound pharmacokinetic differences were observed between comparatively morbid patients with CF and healthy volunteers. These differences could be explained by body weight and body composition for β-lactams with low protein binding. This study aimed to develop a novel population modeling approach to describe the pharmacokinetic differences between both subject groups byThe pharmacokinetics in patients with cystic fibrosis (CF) has long been thought to differ considerably from that in healthy volunteers. For highly protein bound β-lactams, profound pharmacokinetic differences were observed between comparatively morbid patients with CF and healthy volunteers. These differences could be explained by body weight and body composition for β-lactams with low protein binding. This study aimed to develop a novel population modeling approach to describe the pharmacokinetic differences between both subject groups by estimating protein binding. Eight patients with CF (lean body mass [LBM]: 39.8 ± 5.4kg) and six healthy volunteers (LBM: 53.1 ± 9.5kg) received 1027.5 mg cefotiam intravenously. Plasma concentrations and amounts in urine were simultaneously modelled. Unscaled total clearance and volume of distribution were 3% smaller in patients with CF compared to those in healthy volunteers. After allometric scaling by LBM to account for body size and composition, the remaining pharmacokinetic differences were explained by estimating the unbound fraction of cefotiam in plasma. The latter was fixed to 50% in male and estimated as 54.5% in female healthy volunteers as well as 56.3% in male and 74.4% in female patients with CF. This novel approach holds promise for characterizing the pharmacokinetics in special patient populations with altered protein binding.zeige mehrzeige weniger

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Autor(en): Nirav R. Shah, Jürgen B. Bulitta, Martina Kinzig, Cornelia B. Landersdorfer, Yuanyuan Jiao, Dhruvitkumar S. Sutaria, Xun Tao, Rainer Höhl, Ulrike Holzgrabe, Frieder Kees, Ulrich Stephan, Fritz Sörgel
URN:urn:nbn:de:bvb:20-opus-196934
Dokumentart:Artikel / Aufsatz in einer Zeitschrift
Institute der Universität:Fakultät für Chemie und Pharmazie / Institut für Pharmazie und Lebensmittelchemie
Sprache der Veröffentlichung:Englisch
Titel des übergeordneten Werkes / der Zeitschrift (Englisch):Pharmaceutics
ISSN:1999-4923
Erscheinungsjahr:2019
Band / Jahrgang:11
Heft / Ausgabe:6
Aufsatznummer:286
Originalveröffentlichung / Quelle:Pharmaceutics (2019) 11:6, 286. https://doi.org/10.3390/pharmaceutics11060286
DOI:https://doi.org/10.3390/pharmaceutics11060286
Allgemeine fachliche Zuordnung (DDC-Klassifikation):5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften
Freie Schlagwort(e):S-ADAPT; allometric scaling; beta-lactam antibiotics; body composition; body size; cefotiam; cystic fibrosis patients; healthy volunteers; population pharmacokinetics; protein binding
Datum der Freischaltung:29.04.2022
Datum der Erstveröffentlichung:18.06.2019
Lizenz (Deutsch):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International