Is the Pharmacokinetics of First-Line Anti-TB Drugs a Cause of High Mortality Rates in TB Patients Admitted to the ICU? A Non-Compartmental Pharmacokinetic Analysis.
antitubercular agents
biological availability
critical care
ethambutol
intensive care
isoniazid
pharmacokinetics
pyrazinamide
rifampin
tuberculosis
Journal
Tropical medicine and infectious disease
ISSN: 2414-6366
Titre abrégé: Trop Med Infect Dis
Pays: Switzerland
ID NLM: 101709042
Informations de publication
Date de publication:
08 Jun 2023
08 Jun 2023
Historique:
received:
24
02
2023
revised:
28
05
2023
accepted:
02
06
2023
medline:
27
6
2023
pubmed:
27
6
2023
entrez:
27
6
2023
Statut:
epublish
Résumé
Patients with tuberculosis (TB) may develop multi-organ failure and require admission to intensive care. In these cases, the mortality rates are as high as 78% and may be caused by suboptimal serum concentrations of first-line TB drugs. This study aims to compare the pharmacokinetics of oral rifampin, isoniazid, pyrazinamide and ethambutol patients in intensive care units (ICU) to outpatients and to evaluate drug serum concentrations as a potential cause of mortality. A prospective pharmacokinetic (PK) study was performed in Amazonas State, Brazil. The primary PK parameters of outpatients who achieved clinical and microbiological cure were used as a comparative target in a non-compartmental analysis. Thirteen ICU and twenty outpatients were recruited. The clearance and volume of distribution were lower for rifampin, isoniazid, pyrazinamide and ethambutol. ICU thirty-day mortality was 77% versus a cure rate of 89% in outpatients. ICU patients had a lower clearance and volume of distribution for rifampin, isoniazid, pyrazinamide and ethambutol compared to the outpatient group. These may reflect changes to organ function, impeded absorption and distribution to the site of infection in ICU patients and have the potential to impact clinical outcomes.
Sections du résumé
BACKGROUND
BACKGROUND
Patients with tuberculosis (TB) may develop multi-organ failure and require admission to intensive care. In these cases, the mortality rates are as high as 78% and may be caused by suboptimal serum concentrations of first-line TB drugs. This study aims to compare the pharmacokinetics of oral rifampin, isoniazid, pyrazinamide and ethambutol patients in intensive care units (ICU) to outpatients and to evaluate drug serum concentrations as a potential cause of mortality.
METHODS
METHODS
A prospective pharmacokinetic (PK) study was performed in Amazonas State, Brazil. The primary PK parameters of outpatients who achieved clinical and microbiological cure were used as a comparative target in a non-compartmental analysis.
RESULTS
RESULTS
Thirteen ICU and twenty outpatients were recruited. The clearance and volume of distribution were lower for rifampin, isoniazid, pyrazinamide and ethambutol. ICU thirty-day mortality was 77% versus a cure rate of 89% in outpatients.
CONCLUSIONS
CONCLUSIONS
ICU patients had a lower clearance and volume of distribution for rifampin, isoniazid, pyrazinamide and ethambutol compared to the outpatient group. These may reflect changes to organ function, impeded absorption and distribution to the site of infection in ICU patients and have the potential to impact clinical outcomes.
Identifiants
pubmed: 37368730
pii: tropicalmed8060312
doi: 10.3390/tropicalmed8060312
pmc: PMC10303681
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Coordenação de Aperfeicoamento de Pessoal de Nível Superior
ID : 001
Organisme : Fundação de Amparo à Pesquisa do Estado do Amazonas
ID : 002/2018; 005/2019; 004/2020
Organisme : National Health and Medical Research Council-funded Fellowship
ID : APP1142757
Organisme : National Health and Medical Research Council-funded Centre for Research Excellence
ID : APP1044941
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