Drug concentration at the site of disease in children with pulmonary tuberculosis

Autor: Elisa Lopez-Varela, Ahmed A. Abulfathi, Natasha Strydom, Pierre Goussard, Abraham C. van Wyk, Anne Marie Demers, Anneen Van Deventer, Anthony J. Garcia-Prats, Johannes van der Merwe, Matthew Zimmerman, Claire L. Carter, Jacques Janson, Julie Morrison, Helmuth Reuter, Eric H. Decloedt, James A. Seddon, Elin M. Svensson, Rob Warren, Radojka M. Savic, Véronique Dartois, Anneke C. Hesseling
Rok vydání: 2021
Předmět:
Microbiology (medical)
Adult
Antitubercular Agents
Pharmacology and Toxicology
Microbiology
Pharmaceutical Sciences
South Africa
Rare Diseases
1108 Medical Microbiology
Clinical Research
Isoniazid
Tuberculosis
Humans
Pharmacology (medical)
Pharmacology & Pharmacy
Child
Lung
Tuberculosis
Pulmonary
Pharmacology
RIFAMPIN
Pediatric
Science & Technology
Evaluation of treatments and therapeutic interventions
Infant
MIC DISTRIBUTIONS
Pulmonary
Pharmacology and Pharmaceutical Sciences
POPULATION PHARMACOKINETICS
Farmaceutiska vetenskaper
Farmakologi och toxikologi
Pyrazinamide
VARIABILITY
lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4]
Orphan Drug
Infectious Diseases
Medical Microbiology
6.1 Pharmaceuticals
HIV/AIDS
MYCOBACTERIUM-TUBERCULOSIS
Patient Safety
1115 Pharmacology and Pharmaceutical Sciences
Infection
Life Sciences & Biomedicine
Ethambutol
0605 Microbiology
Zdroj: The Journal of antimicrobial chemotherapy, vol 77, iss 6
Journal of Antimicrobial Chemotherapy, 77, 1710-1719
Journal of Antimicrobial Chemotherapy, 77, 6, pp. 1710-1719
ISSN: 1460-2091
1710-1719
0305-7453
Popis: Background Current TB treatment for children is not optimized to provide adequate drug levels in TB lesions. Dose optimization of first-line antituberculosis drugs to increase exposure at the site of disease could facilitate more optimal treatment and future treatment-shortening strategies across the disease spectrum in children with pulmonary TB. Objectives To determine the concentrations of first-line antituberculosis drugs at the site of disease in children with intrathoracic TB. Methods We quantified drug concentrations in tissue samples from 13 children, median age 8.6 months, with complicated forms of pulmonary TB requiring bronchoscopy or transthoracic surgical lymph node decompression in a tertiary hospital in Cape Town, South Africa. Pharmacokinetic models were used to describe drug penetration characteristics and to simulate concentration profiles for bronchoalveolar lavage, homogenized lymph nodes, and cellular and necrotic lymph node lesions. Results Isoniazid, rifampicin and pyrazinamide showed lower penetration in most lymph node areas compared with plasma, while ethambutol accumulated in tissue. None of the drugs studied was able to reach target concentration in necrotic lesions. Conclusions Despite similar penetration characteristics compared with adults, low plasma exposures in children led to low site of disease exposures for all drugs except for isoniazid.
Databáze: OpenAIRE
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