Should Airway Interstitial Fluid Be Used to Evaluate the Pharmacokinetics of Macrolide Antibiotics for Dose Regimen Determination in Respiratory Infection?

Content Provider	Europe PMC
Author	Wang, Jianzhong Zhou, Xueying Elazab, Sara T. Park, Seung-Chun Hsu, Walter H.
Editor	Kovács, Dóra
Copyright Year	2023
Abstract	Macrolide antibiotics are important drugs to combat infections. The pharmacokinetics (PK) of these drugs are essential for the determination of their optimal dose regimens, which affect antimicrobial pharmacodynamics and treatment success. For most drugs, the measurement of their concentrations in plasma/serum is the surrogate for drug concentrations in target tissues for therapy. However, for macrolides, simple reliance on total or free drug concentrations in serum/plasma might be misleading. The macrolide antibiotic concentrations of serum/plasma, interstitial fluid (ISF), and target tissue itself usually yield very different PK results. In fact, the PK of a macrolide antibiotic based on serum/plasma concentrations alone is not an ideal predictor for the in vivo efficacy against respiratory pathogens. Instead, the PK based on drug concentrations at the site of infection or ISF provide much more clinically relevant information than serum/plasma concentrations. This review aims to summarize and compare/discuss the use of drug concentrations of serum/plasma, airway ISF, and tissues for computing the PK of macrolides. A better understanding of the PK of macrolide antibiotics based on airway ISF concentrations will help optimize the antibacterial dose regimen as well as minimizing toxicity and the emergence of drug resistance in clinical practice.
Journal	Antibiotics (Basel, Switzerland)
Volume Number	12
PubMed Central reference number	PMC10135031
Issue Number	4
PubMed reference number	37107062
e-ISSN	20796382
DOI	10.3390/antibiotics12040700
Language	English
Publisher	MDPI
Publisher Date	2023-04-03
Access Restriction	Open
Rights License	Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). © 2023 by the authors.
Subject Keyword	serum/plasma concentrations interstitial concentrations tissue concentrations pharmacokinetics macrolide antibiotics
Content Type	Text
Resource Type	Article
Subject	Biochemistry Pharmacology, Toxicology and Pharmaceutics Microbiology Pharmacology (medical) Infectious Diseases Microbiology (medical)