PBPK Modeling and Simulation of Antibiotics Amikacin, Gentamicin, Tobramycin, and Vancomycin Used in Hospital Practice
| Autor: | José Carlos Oliveira, Rui A. S. Lapa, Nuno Vale, Helena Martins, Abigail Ferreira |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Physiologically based pharmacokinetic modelling
medicine.medical_specialty medicine.drug_class therapeutic drug monitoring Science vancomycin Population Antibiotics tobramycin gentamicin Article General Biochemistry Genetics and Molecular Biology amikacin medicine Tobramycin education Intensive care medicine Ecology Evolution Behavior and Systematics education.field_of_study PBPK modeling medicine.diagnostic_test business.industry Paleontology GastroPlus™ Space and Planetary Science Amikacin Therapeutic drug monitoring antibiotics use Vancomycin Gentamicin business medicine.drug |
| Zdroj: | Life, Vol 11, Iss 1130, p 1130 (2021) Life; Volume 11; Issue 11; Pages: 1130 Life |
| ISSN: | 2075-1729 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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