Academic Bibliography

 Search 200 years of publications by Ghent University researchers.
Advanced search
1 file | 1.00 MB
Add to list
  1. Search results
  2. Altered intravenous drug disposition ...

Altered intravenous drug disposition in people living with cystic fibrosis : a meta‐analysis integrating top‐down and bottom‐up data

Pieter-Jan De Sutter (UGent) , Maxime Van Haeverbeke (UGent) , Eva Van Braeckel (UGent) , Stephanie Van Biervliet (UGent) , Jan Van Bocxlaer (UGent) , An Vermeulen (UGent) and Elke Gasthuys (UGent)
(2022) CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY. 11(8). p.951-966
Author
Organization
Abstract
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-down) and the pathophysiological parameters known to affect pharmacokinetics (PKs; bottom-up). This was done through meta-analyses and meta-regressions 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-by-case basis.
Keywords
ARYLAMINE N-ACETYLTRANSFERASE, XANTHINE-OXIDASE, BODY-COMPOSITION, ADULT PATIENTS, PHARMACOKINETICS, CLEARANCE, BIAS, ADIPONECTIN, INVOLVEMENT, POPULATION

Downloads

  • Download
    published.pdf
    • full text (Published version)
    • |
    • open access
    • |
    • PDF
    • |
    • 1.00 MB

Citation

Please use this url to cite or link to this publication:

MLA
De Sutter, Pieter-Jan, et al. “Altered Intravenous Drug Disposition in People Living with Cystic Fibrosis : A Meta‐analysis Integrating Top‐down and Bottom‐up Data.” CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY, vol. 11, no. 8, 2022, pp. 951–66, doi:10.1002/psp4.12832.
APA
De Sutter, P.-J., Van Haeverbeke, M., Van Braeckel, E., Van Biervliet, S., Van Bocxlaer, J., Vermeulen, A., & Gasthuys, E. (2022). Altered intravenous drug disposition in people living with cystic fibrosis : a meta‐analysis integrating top‐down and bottom‐up data. CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY, 11(8), 951–966. https://doi.org/10.1002/psp4.12832
Chicago author-date
De Sutter, Pieter-Jan, Maxime Van Haeverbeke, Eva Van Braeckel, Stephanie Van Biervliet, Jan Van Bocxlaer, An Vermeulen, and Elke Gasthuys. 2022. “Altered Intravenous Drug Disposition in People Living with Cystic Fibrosis : A Meta‐analysis Integrating Top‐down and Bottom‐up Data.” CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY 11 (8): 951–66. https://doi.org/10.1002/psp4.12832.
Chicago author-date (all authors)
De Sutter, Pieter-Jan, Maxime Van Haeverbeke, Eva Van Braeckel, Stephanie Van Biervliet, Jan Van Bocxlaer, An Vermeulen, and Elke Gasthuys. 2022. “Altered Intravenous Drug Disposition in People Living with Cystic Fibrosis : A Meta‐analysis Integrating Top‐down and Bottom‐up Data.” CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY 11 (8): 951–966. doi:10.1002/psp4.12832.
Vancouver
1.
De Sutter P-J, Van Haeverbeke M, Van Braeckel E, Van Biervliet S, Van Bocxlaer J, Vermeulen A, et al. Altered intravenous drug disposition in people living with cystic fibrosis : a meta‐analysis integrating top‐down and bottom‐up data. CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY. 2022;11(8):951–66.
IEEE
[1]
P.-J. De Sutter et al., “Altered intravenous drug disposition in people living with cystic fibrosis : a meta‐analysis integrating top‐down and bottom‐up data,” CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY, vol. 11, no. 8, pp. 951–966, 2022.
@article{8760495,
  abstract     = {{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-down) and the pathophysiological parameters known to affect pharmacokinetics (PKs; bottom-up). This was done through meta-analyses and meta-regressions 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-by-case basis.}},
  author       = {{De Sutter, Pieter-Jan and Van Haeverbeke, Maxime and Van Braeckel, Eva and Van Biervliet, Stephanie and Van Bocxlaer, Jan and Vermeulen, An and Gasthuys, Elke}},
  issn         = {{2163-8306}},
  journal      = {{CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY}},
  keywords     = {{ARYLAMINE N-ACETYLTRANSFERASE,XANTHINE-OXIDASE,BODY-COMPOSITION,ADULT PATIENTS,PHARMACOKINETICS,CLEARANCE,BIAS,ADIPONECTIN,INVOLVEMENT,POPULATION}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{951--966}},
  title        = {{Altered intravenous drug disposition in people living with cystic fibrosis : a meta‐analysis integrating top‐down and bottom‐up data}},
  url          = {{http://doi.org/10.1002/psp4.12832}},
  volume       = {{11}},
  year         = {{2022}},
}
Altmetric
View in Altmetric
Web of Science
Times cited: