The pharmacokinetics of antibiotics in cystic fibrosis

Dosing of antibiotics in people with cystic fibrosis (CF) is challenging, due to altered pharmacokinetics, difficulty of lung tissue penetration, and increasing presence of antimicrobial resistance. The purpose of this work is to critically review original data as well as previous reviews and guidel...

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Published in:Expert opinion on drug metabolism & toxicology Vol. 17; no. 1; pp. 53 - 68
Main Authors: Akkerman-Nijland, Anne M., Akkerman, Onno W., Grasmeijer, Floris, Hagedoorn, Paul, Frijlink, Henderik. W., Rottier, Bart. L., Koppelman, Gerard. H., Touw, Daniel. J.
Format: Journal Article
Language:English
Published: England Taylor & Francis 02.01.2021
Subjects:
Administration, Inhalation
Adult
Anti-Bacterial Agents - administration & dosage
Anti-Bacterial Agents - pharmacokinetics
Antibiotics
Body Weight
Child
cystic fibrosis
Cystic Fibrosis - drug therapy
Cystic Fibrosis - physiopathology
Dose-Response Relationship, Drug
drug disposition
Humans
pharmacodynamics
pharmacokinetics
Practice Guidelines as Topic
Tissue Distribution
drug disposition
pharmacokinetics
Antibiotics
cystic fibrosis
pharmacodynamics
ISSN:1742-5255, 1744-7607, 1744-7607
Online Access:Get full text
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Summary:Dosing of antibiotics in people with cystic fibrosis (CF) is challenging, due to altered pharmacokinetics, difficulty of lung tissue penetration, and increasing presence of antimicrobial resistance. The purpose of this work is to critically review original data as well as previous reviews and guidelines on pharmacokinetics of systemic and inhaled antibiotics in CF, with the aim to propose strategies for optimization of antibacterial therapy in both children and adults with CF. For systemic antibiotics, absorption is comparable in CF patients and non-CF controls. The volume of distribution (Vd) of most antibiotics is similar between people with CF with normal body composition and healthy individuals. However, there are a few exceptions, like cefotiam and tobramycin. Many antibiotic class-dependent changes in drug metabolism and excretion are reported, with an increased total body clearance for ß-lactam antibiotics, aminoglycosides, fluoroquinolones, and trimethoprim. We, therefore, recommend following class-specific guidelines for CF, mostly resulting in higher dosages per kg bodyweight in CF compared to non-CF controls. Higher local antibiotic concentrations in the airways can be obtained by inhalation therapy, with which eradication of bacteria may be achieved while minimizing systemic exposure and risk of toxicity.
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ISSN:1742-5255
1744-7607
1744-7607
DOI:10.1080/17425255.2021.1836157