Estimation of Anti Tubercular Drug levels in human plasma and Correlation with Clinical Outcome in Indian Patients

Abstract

People diagnosed with drug sensitive tuberculosis (DSTB) typically receive a standard newlinefirst-line drugs of fixed-dose combination (FDC) daily regimen as widely newlinerecommended by WHO. Based on WHO s recommendations, Maharashtra, shifted newlinefrom an intermittent to a daily fixed dose combination antitubercular regimen. While newlinefailure rates are generally low, several reports have documented recurrence rates of 12 newlineto 15%, while multidrug resistance rates among previously treated patients vary from newline12 to 17%, indicating that the treatment results in the incomplete sterilization of lesions newlinedue to subtherapeutic concentrations of firstline drugs. Studies correlating plasma drug newlinelevels with clinical outcome and adverse reactions of the currently used FDC daily newlineregimen of anti-TB drugs are unavailable under programmatic settings (DOTS Center), newlineso understanding of therapeutic drug monitoring in tuberculosis is of conflicting newlineopinion. Hence, a study was required to understand drug plasma correlation with the newlineclinical outcome to identify the need of monitoring of antitubercular FDC daily regimen newlineunder programmatic settings. newlineAIM: newlineTo estimate the first line anti-tubercular drug levels in human plasma and correlate with newlineclinical outcome in Indian patients newlineOBJECTIVES: newlinei. To develop and establish a simple, reliable and validated bioanalytical method for newlinesimultaneous estimation of first-line antitubercular drugs isoniazid, rifampicin, newlinepyrazinamide and ethambutol in human plasma samples by LC-MS/MS. newlineii. To estimate 2 and 6 hour plasma concentrations of the first-line antitubercular newlinedrugs isoniazid, rifampicin, pyrazinamide and ethambutol in a cohort of patients newlinedigossed drug sensitive tuberculosis in programmatic setting and to determine the newlinerelationship between the concentrations and the clinical outcome.