ABSTRACT
Background: Poor response to TB therapy might be attributable to subtherapeutic levels in drug-compliant patients. Pharmacokinetic parameters can be affected by comorbidities or the interaction of drugs with food. Objectives: This study aimed to determine the effect of food intake upon pharmacokinetics of rifampicin and isoniazid in a Peruvian population with TB. Methods: Rifampicin and isoniazid levels were analysed at 2, 4 and 6 h after drug intake in both fasting and non-fasting states using LC-MS methods. Results: Sixty patients participated in the study. The median rifampicin Cmax and AUC0-6 were higher during fasting than non-fasting: 7.02 versus 6.59 mg/L (P = 0.054) and 28.64 versus 24.31 mg·h/L (P = 0.002). There was a statistically significant delay overall of non-fasting Tmax compared with the fasting state Tmax (P = 0.005). In the multivariate analysis, besides the effect of fasting, Cmax for females was 20% higher than for males (P = 0.03). Concerning isoniazid, there were significant differences in the Cmax during non-fasting (median = 3.51 mg/L) compared with fasting (4.54 mg/L). The isoniazid dose received had an effect upon the isoniazid levels (1.26, P = 0.038). In the multivariate analysis, isoniazid exposure during fasting was found to be 14% higher than during non-fasting (CI = 1.02-1.28, P < 0.001). Neither radiological extent of the disease nor consumption of food with drug intake nor pharmacokinetics of rifampicin or isoniazid was associated with a poorer treatment outcome. Conclusions: Rifampicin in particular and isoniazid pharmacokinetics were significantly affected by the intake of the drug with food between and within individuals.
Subject(s)
Antitubercular Agents/pharmacokinetics , Eating , Food-Drug Interactions , Isoniazid/pharmacokinetics , Rifampin/pharmacokinetics , Tuberculosis, Pulmonary/drug therapy , Adult , Biological Variation, Individual , Fasting , Female , Humans , Male , Middle Aged , Multivariate Analysis , Treatment Outcome , Young AdultABSTRACT
Poor response to tuberculosis (TB) therapy might be attributable to subtherapeutic levels in drug-compliant patients. Pharmacokinetic (PK) parameters can be affected by several factors, such as comorbidities or the interaction of TB drugs with food. This study aimed to determine the PK of isoniazid (INH) in a Peruvian TB population under observed daily and twice-weekly (i.e., biweekly) therapy. Isoniazid levels were analyzed at 2 and 6 h after drug intake using liquid chromatography mass spectrometric methods. A total of 107 recruited patients had available PK data; of these 107 patients, 42.1% received biweekly isoniazid. The mean biweekly dose (12.8 mg/kg of body weight/day) was significantly lower than the nominal dose of 15 mg/kg/day (P < 0.001), and this effect was particularly marked in patients with concurrent diabetes and in males. The median maximum plasma concentration (Cmax) and area under the concentration-time curve from 0 to 6 h (AUC0-6) were 2.77 mg/liter and 9.71 mg · h/liter, respectively, for daily administration and 8.74 mg/liter and 37.8 mg · h/liter, respectively, for biweekly administration. There were no differences in the Cmax with respect to gender, diabetes mellitus (DM) status, or HIV status. Food was weakly associated with lower levels of isoniazid during the continuation phase. Overall, 34% of patients during the intensive phase and 33.3% during the continuation phase did not reach the Cmax reference value. However, low levels of INH were not associated with poorer clinical outcomes. In our population, INH exposure was affected by weight-adjusted dose and by food, but comorbidities did not indicate any effect on PK. We were unable to demonstrate a clear relationship between the Cmax and treatment outcome in this data set. Twice-weekly weight-adjusted dosing of INH appears to be quite robust with respect to important potentially influential patient factors under program conditions.
Subject(s)
Antitubercular Agents/pharmacokinetics , Dietary Fats/pharmacokinetics , Food-Drug Interactions , Isoniazid/pharmacokinetics , Rifampin/pharmacokinetics , Tuberculosis, Pulmonary/drug therapy , Adolescent , Adult , Anti-HIV Agents/therapeutic use , Antitubercular Agents/therapeutic use , Area Under Curve , Comorbidity , Diabetes Mellitus/drug therapy , Diabetes Mellitus/epidemiology , Diabetes Mellitus/pathology , Dietary Fats/metabolism , Drug Administration Schedule , Female , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/pathology , Humans , Hypoglycemic Agents/therapeutic use , Isoniazid/therapeutic use , Male , Middle Aged , Peru/epidemiology , Rifampin/therapeutic use , Sex Factors , Treatment Outcome , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/pathologyABSTRACT
To evaluate the risk of tuberculosis (TB) infection, the General Directorate of Epidemiology of the Ministry of Health developed a sentinel surveillance system in health centers located in the Constitutional Province of Callao. This surveillance system included the diagnosis of latent tuberculosis infection (LTI) using interferon gamma release assays. The objective of the present study was to estimate the prevalence of LTI in health workers in a region with a high burden of TB. The prevalence of LTI in health workers was 56%. The prevalence of LTI was 63% in workers with more than 10 years of service and 58-60% in workers with more than 35 years of service. The prevalence of LTI in health workers from primary health care centers was high, and longer service time was one of the main risk factors.
Con el propósito de disponer de información sobre los riesgos para infección por tuberculosis, la Dirección General de Epidemiología del Ministerio de Salud, desarrolló una vigilancia centinela en establecimientos de salud de la Provincia constitucional del Callao, dicha vigilancia incluyó el diagnóstico de infección tuberculosa latente (ITL) mediante la aplicación del método IGRA. El objetivo del presente estudio fue estimar la prevalencia de ITL en trabajadores de salud de un área con alta carga de enfermedad de tuberculosis. La prevalencia de ITL en trabajadores de salud fue 56%. En trabajadores con más de 10 años de servicio la prevalencia se incrementó a 63% y en trabajadores con más de 35 años de servicio se encontraron prevalencias entre 58 y 60%. Existe una alta prevalencia de ITL en trabajadores de salud de establecimientos del primer nivel de atención, identificándose al mayor tiempo de servicio, como uno de los principales factores de riesgo.
Subject(s)
Health Personnel , Latent Tuberculosis/epidemiology , Adult , Aged , Female , Health Facilities , Humans , Male , Middle Aged , Peru/epidemiology , Prevalence , Primary Health Care , Risk Factors , Urban Health , Young AdultABSTRACT
RESUMEN Con el propósito de disponer de información sobre los riesgos para infección por tuberculosis, la Dirección General de Epidemiología del Ministerio de Salud, desarrolló una vigilancia centinela en establecimientos de salud de la Provincia constitucional del Callao, dicha vigilancia incluyó el diagnóstico de infección tuberculosa latente (ITL) mediante la aplicación del método IGRA. El objetivo del presente estudio fue estimar la prevalencia de ITL en trabajadores de salud de un área con alta carga de enfermedad de tuberculosis. La prevalencia de ITL en trabajadores de salud fue 56%. En trabajadores con más de 10 años de servicio la prevalencia se incrementó a 63% y en trabajadores con más de 35 años de servicio se encontraron prevalencias entre 58 y 60%. Existe una alta prevalencia de ITL en trabajadores de salud de establecimientos del primer nivel de atención, identificándose al mayor tiempo de servicio, como uno de los principales factores de riesgo.
ABSTRACT To evaluate the risk of tuberculosis (TB) infection, the General Directorate of Epidemiology of the Ministry of Health developed a sentinel surveillance system in health centers located in the Constitutional Province of Callao. This surveillance system included the diagnosis of latent tuberculosis infection (LTI) using interferon gamma release assays. The objective of the present study was to estimate the prevalence of LTI in health workers in a region with a high burden of TB. The prevalence of LTI in health workers was 56%. The prevalence of LTI was 63% in workers with more than 10 years of service and 58-60% in workers with more than 35 years of service. The prevalence of LTI in health workers from primary health care centers was high, and longer service time was one of the main risk factors.