ABSTRACT
BACKGROUND: Dried blood spot (DBS) sampling for pharmacokinetic (PK) studies and therapeutic drug monitoring have unique advantages over venous sampling. This study aimed to evaluate a DBS method for first-line anti-tuberculosis drugs in children, and DBS sampling to assess PK parameters. METHODS: Paraguayan children were treated according to the revised paediatric dosing scheme of the World Health Organization. A PK curve was performed both with DBS sampling and conventional venous sampling for rifampicin, pyrazinamide and ethambutol. Passing-Bablok regression, Bland-Altman plots and predictive performance evaluation were used to assess agreement between DBS and plasma concentrations. The percentages of patients attaining population PK values for Cmax and AUC0-24h were calculated. RESULTS: After use of a conversion factor, Passing-Bablok regression showed no significant proportional or systematic bias between DBS and plasma concentrations. Bland-Altman plots showed that 95% of the ratios of the DBS predicted:observed plasma concentrations lay between 0.6 and 1.4 for rifampicin, 0.5 and 1.6 for pyrazinamide and -0.4 and 2.8 for ethambutol. DBS measurements showed acceptable predictive performance for rifampicin and pyrazinamide, but not for ethambutol. Assessment of Cmax target attainment was 62.5% for isoniazid, 25% for rifampicin, 100% for pyrazinamide and 75% for ethambutol. CONCLUSION: For rifampicin and pyrazinamide, the DBS method was accurate in predicting plasma concentrations, and was used successfully for PK parameter assessment. However, predicting ethambutol plasma concentrations with DBS measurement was associated with too much imprecision. Despite higher dosing, only 25% of the population reached average target adult rifampicin exposures.
Subject(s)
Antitubercular Agents/pharmacokinetics , Antitubercular Agents/therapeutic use , Dried Blood Spot Testing/methods , Drug Monitoring/methods , Adolescent , Antitubercular Agents/blood , Child , Child, Preschool , Ethambutol/blood , Ethambutol/pharmacokinetics , Ethambutol/therapeutic use , Female , Humans , Infant , Male , Pyrazinamide/blood , Pyrazinamide/pharmacokinetics , Pyrazinamide/therapeutic use , Rifampin/blood , Rifampin/pharmacokinetics , Rifampin/therapeutic use , Tuberculosis/drug therapyABSTRACT
INTRODUCTION: Tuberculosis (TB) is the leading cause of death due to an infectious disease worldwide. Especially in low-income countries, new diagnostic techniques that are accessible, inexpensive and easy-to-use, are needed to shorten transmission time and initiate treatment earlier. OBJECTIVE: We conducted a study with a handheld, point-of-care electronic nose (eNose) device to diagnose TB through exhaled breath. SETTING: This study includes a total of 110 patients and visitors of an expert centre of respiratory diseases in Asunción, Paraguay. TB diagnosis was established by culture of Mycobacterium tuberculosis complex and compared with the eNose results in two phases. RESULTS: The calibration phase, including only culture confirmed TB cases versus healthy people, demonstrated a sensitivity and specificity of 91% and 93% respectively. The confirmation phase, including all participants, showed a sensitivity of 88% and a specificity of 92%. The eNose showed high acceptance rate among participants, and was easy to operate. CONCLUSION: The eNose resulted in a powerful technique to differentiate between healthy people and TB patients. Its comfort, speed and usability promise great potential in vulnerable groups, in remote areas and hospital settings to triage patients with suspicion of TB.
