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

Tropical Medicine and Infectious Disease

article

Francisco Beraldi-Magalhaes¹  Suzanne L. Parker⁵  Cristina Sanches⁶  Leandro Sousa Garcia¹  Brenda Karoline Souza Carvalho¹  Amanda Araujo Costa²  Mariana Millan Fachi⁷  Marcus Vinicius de Liz⁸  Alexandra Brito de Souza¹  Izabella Picinin Safe²  Roberto Pontarolo⁷  Steven Wallis⁵  Jeffrey Lipman⁵  Jason A. Roberts⁵  Marcelo Cordeiro-Santos¹ 

[1] Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas;Fundação de Medicina Tropical Doutor Heitor Vieira Dourado;Secretaria de Estado da Saúde do Paraná;School of Medicine;UQ Centre for Clinical Research, The University of Queensland;Department of Pharmacy, Campus Centro-Oeste Dona Lindu, Universidade Federal de São João del-Rei;Department of Pharmacy, Campus Jardim Botânico, Universidade Federal do Paraná;Department of Chemistry & Biology, Campus Curitiba, Universidade Tecnológica Federal do Paraná;Department of Intensive Care Medicine, Royal Brisbane and Women’s Hospital;Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier;Department of Pharmacy, Royal Brisbane and Women’s Hospital;School of Medicine, Universidade Nilton Lins

关键词: tuberculosis;    antitubercular agents;    rifampin;    isoniazid;    pyrazinamide;    ethambutol;    pharmacokinetics;    biological availability;    intensive care;    critical care;   

DOI  :  10.3390/tropicalmed8060312

学科分类：社会科学、人文和艺术（综合）

来源: mdpi

【 摘 要 】

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: 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: 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: 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.

【 授权许可】

CC BY