Shah, Nirav R. and Bulitta, Juergen B. and Kinzig, Martina and Landersdorfer, Cornelia B. and Jiao, Yuanyuan and Sutaria, Dhruvitkumar S. and Tao, Xun and Hoehl, Rainer and Holzgrabe, Ulrike and Kees, Frieder and Stephan, Ulrich and Soergel, Fritz (2019) Novel Population Pharmacokinetic Approach to Explain the Differences between Cystic Fibrosis Patients and Healthy Volunteers via Protein Binding. PHARMACEUTICS, 11 (6). ISSN 1999-4923,
Full text not available from this repository. (Request a copy)Abstract
The pharmacokinetics in patients with cystic fibrosis (CF) has long been thought to differ considerably from that in healthy volunteers. For highly protein bound beta -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 beta -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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GLOMERULAR-FILTRATION-RATE; RENAL CLEARANCE; PHARMACODYNAMIC BREAKPOINTS; NONLINEAR PHARMACOKINETICS; ANTIBIOTIC-PROPHYLAXIS; CEFOTIAM; DISPOSITION; PLASMA; PIPERACILLIN; SERUM; cystic fibrosis patients; healthy volunteers; cefotiam; beta-lactam antibiotics; population pharmacokinetics; protein binding; allometric scaling; body size; body composition; S-ADAPT |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmacology and Toxicology (Prof. Schlossmann, formerly Prof. Seifert) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Apr 2020 05:39 |
| Last Modified: | 14 Apr 2020 05:39 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26875 |
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