The Indian Revised National Tuberculosis (TB) Control Programme uses thrice-weekly treatment with standard drug dosages. The role of plasma drug levels and other factors in determining TB treatment outcomes is not well understood. We aimed to determine the factors influencing the concentrations of rifampin (RMP), isoniazid (INH), and pyrazinamide (PZA) at 2 h postdosing in adult TB patients and to study the factors impacting TB treatment outcome. We recruited 1,912 adult TB patients (newly treated and retreated patients) with pulmonary/extrapulmonary TB receiving antitubercular treatment (ATT) in the RNTCP in Chennai, India. At steady state, the concentrations of RMP, INH, and PZA were determined at 2 h postdosing after supervised drug administration. A total of 1,648 patients had a favorable outcome, while 264 (14%) had an unfavorable outcome. A total of 91%, 16%, and 17% of the patients had suboptimal concentrations of RMP (Ͻ8 g/ml), INH (Ͻ3 g/ml), and PZA (Ͻ20 g/ml), respectively. Factors associated with treatment outcome were low RMP concentrations (adjusted odds ratio [aOR], 0.94; 95% confidence interval [CI], 0.89 to 0.99; P ϭ 0.036), category II ATT (aOR, 2.39; 95% CI, 1.56 to 3.65; P Ͻ 0.001), low body weight (aOR, 0.96; 95% CI, 0.94 to 0.98; P Ͻ 0.001), alcohol use (aOR, 2.17; 95% CI, 1.42 to 3.31; P Ͻ 0.001), male gender (aOR, 1.92; 95% CI, 1.02 to 3.62; P ϭ 0.043), and baseline INH resistance (aOR, 5.74; 95% CI, 3.12 to 10.59; P Ͻ 0.001), which significantly increased the likelihood of an unfavorable outcome in multivariate logistic regression analysis. Further studies are needed to optimize anti-TB drug dosages and improve cure rates. Drug susceptibility testing at the baseline and attention to undernutrition and alcohol dependence are other important interventions.

Nevirapine blood concentrations are affected by many factors, most notably age ≤ 3 years; a combination of young age, stunting and CYP2B6 GG or GT genotype could potentially result in sub-therapeutic nevirapine concentrations. Dosing recommendations for children should be reviewed in the light of these findings.

Background The relationships between first-line drug concentrations and clinically important outcomes among patients with tuberculosis (TB) remain poorly understood. Methods We enrolled a prospective cohort of patients with new pulmonary TB receiving thrice-weekly treatment in India. The maximum plasma concentration of each drug was determined at months 1 and 5 using blood samples drawn 2 hours postdose. Subtherapeutic cutoffs were: rifampicin <8 µg/mL, isoniazid <3 µg/mL, and pyrazinamide <20 µg/mL. Factors associated with lower log-transformed drug concentrations, unfavorable outcomes (composite of treatment failure, all-cause mortality, and recurrence), and individual outcomes were examined using Poisson regression models. Results Among 404 participants, rifampicin, isoniazid, and pyrazinamide concentrations were subtherapeutic in 85%, 29%, and 13%, respectively, at month 1 (with similar results for rifampicin and isoniazid at month 5). Rifampicin concentrations were lower with human immunodeficiency virus coinfection (median, 1.6 vs 4.6 µg/mL; P = .015). Unfavorable outcome was observed in 19%; a 1-μg/mL decrease in rifampicin concentration was independently associated with unfavorable outcome (adjusted incidence rate ratio [aIRR], 1.21 [95% confidence interval {CI}, 1.01–1.47]) and treatment failure (aIRR, 1.16 [95% CI, 1.05–1.28]). A 1-μg/mL decrease in pyrazinamide concentration was associated with recurrence (aIRR, 1.05 [95% CI, 1.01–1.11]). Conclusions Rifampicin concentrations were subtherapeutic in most Indian patients taking a thrice-weekly TB regimen, and low rifampicin and pyrazinamide concentrations were associated with poor outcomes. Higher or more frequent dosing is needed to improve TB treatment outcomes in India.

Objectives Tuberculosis continues to be a major public health problem globally, despite incredible advancements in healthcare system. In Unani system of medicine, Qurs Tabasheer Sarthani (QTS) and Arq Hara Bhara (AHB) have been traditionally used for tuberculosis like conditions. The study was aimed to investigate the effects of co-administration of QTS and AHB with category I first line antitubercular drugs (CAT-I) on the indices of liver and kidney function in rats. Methods QTS and AHB were prepared individually and mixed to achieve final compound Unani pharmacopoeia formulation (UPF). The human equivalent doses for rats were calculated and administered with and without CAT-I. The effects of the formulations on serum indices of kidney and liver function, hematological markers and plasma CAT-I drug levels were estimated at 14th, 60th & 180th days of treatment. Results The administration of UPF, CAT-I and UPF + CAT-I altered the levels of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma glutamyltransferase (GGT) and haematological markers. These alterations were within permissible range and randomly distributed among groups during various time points. Administration of CAT-I alone resulted in moderate histopathological changes which were completely abrogated in CAT-I + UPF co-administered animals. The co-administration of UPF with CAT-I improved the plasma peak rifampicin (RIF) levels, without altering the liver and kidney functions. Conclusions The co-administration of UPF with ATT improved liver and kidney functions and increased the plasma levels of RIF. These beneficial findings provide a scope to evaluate the pharmacokinetic studies in humans.