PBPK Modeling and Simulation of Antibiotics Amikacin, Gentamicin, Tobramycin, and Vancomycin Used in Hospital Practice

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Ferreira, A (Author) Other; Martins, H (Author) Other; Oliveira, JC (Author) Other; Lapa, R (Author) Other; Nuno Vale (Author) FMUP

Journal

Title: LIFE-BASEL

Vol. 11

Final page: 1130

ISSN: 2075-1729

Publisher: MDPI

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 0 Citations

Other information

Authenticus ID: P-00V-JE4

DOI: 10.3390/life11111130

Abstract (EN): The importance of closely observing patients receiving antibiotic therapy, performing therapeutic drug monitoring (TDM), and regularly adjusting dosing regimens has been extensively demonstrated. Additionally, antibiotic resistance is a contemporary concerningly dangerous issue. Optimizing the use of antibiotics is crucial to ensure treatment efficacy and prevent toxicity caused by overdosing, as well as to combat the prevalence and wide spread of resistant strains. Some antibiotics have been selected and reserved for the treatment of severe infections, including amikacin, gentamicin, tobramycin, and vancomycin. Critically ill patients often require long treatments, hospitalization, and require particular attention regarding TDM and dosing adjustments. As these antibiotics are eliminated by the kidneys, critical deterioration of renal function and toxic effects must be prevented. In this work, clinical data from a Portuguese cohort of 82 inpatients was analyzed and physiologically based pharmacokinetic (PBPK) modeling and simulation was used to study the influence of different therapeutic regimens and parameters as biological sex, body weight, and renal function on the biodistribution and pharmacokinetic (PK) profile of these four antibiotics. Renal function demonstrated the greatest impact on plasma concentration of these antibiotics, and vancomycin had the most considerable accumulation in plasma over time, particularly in patients with impaired renal function. Thus, through a PBPK study, it is possible to understand which pharmacokinetic parameters will have the greatest variation in a given population receiving antibiotic administrations in hospital context.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 15