The Department of Clinical Pharmacology has been actively involved in conducting pharmacokinetic and bioavailability studies of anti-TB and antiretroviral drugs in TB and HIV-TB patients. NIRT is one of the very few institutes in India that has validated methods for the estimation of anti-TB (first-line and second-line), anti-retroviral and anti-diabetic drugs by HPLC. Clinical Pharmacology laboratory participates in the International Quality Assurance Program (Netherlands) for drug estimations. The studies carried out addressed key research issues, namely, drug interactions, impact of HIV infection on anti-TB drug levels, significance of pharmacogenetics in relation to TB and HIV and pediatric studies. Most studies are the first of its kind in India. They have come out with important findings and provided evidence to the National Programs in India. In addition, this laboratory serves the patient community by undertaking anti-TB drug estimations upon requests from neighbouring hospitals as well as from other states. The Department of Clinical Pharmacology has gained lot of visibility nationally and internationally and are being approached for collaborations in the area of pharmacokinetics of anti-TB and anti-retroviral drugs.

Research Focus

•  Pharmacokinetics of anti-TB, anti-diabetic and antiretroviral drugs in adults
    and children

•  Anti-TB drug estimations in the ongoing Clinical Trials

•  Method development for newer molecules

New Initiatives

•  Pharmacokinetics of second-line anti-TB drugs in children and adolescents
    with MDR TB

•  Pharmacokinetics of second line drugs in adult patients with MDR-TB

•  Drug- drug interactions between first line anti-TB and anti-diabetic drugs

•  Bioavailability of first line anti-TB drugs in pulmonary TB patients

•  Impact of pregnancy on Tuberculosis

•  Therapeutic drug monitoring in drug sensitive, non-responding Pulmonary TB     patients

•  Pharmacokinetics of first line anti-TB in adult TB patients: The salient finding of this study are: 1) Sub therapeutic RMP concentrations is the key risk factor for an unfavorable TB treatment outcome. 2) Food lowered anti-TB drug concentrations significantly and delayed absorption. 3) TB patients with Diabetes mellitus (DM) had lower INH and PZA concentrations 4) Genotyping of TB patients for NAT2 gene polymorphism revealed that 58% of the study population comprised slow acetylators.

•  Pharmacokinetic study of rifabutin: The study showed that peak rifabutin concentration was below the lower therapeutic limit (< 0.3µg/ml) in a high proportion of patients, suggesting the need to increase rifabutin dose. Consequent to this study, the programme has increased the rifabutin dose during ritonavir co-administration to 300mg thrice weekly. Subsequently another study was conducted on the dose related pharmacokinetics of rifabutin using 150 mg daily versus 300 mg thrice weekly and it was observed either dose can be used.

•  Rifampicin exposure is lower in HIV-infected TB patients receiving intermittent than daily anti-tuberculosis treatment: Patients treated with a thrice – weekly regimen had significantly lower plasma peak concentration, exposure and higher oral clearance of RMP than those treated with the daily regimen.

•  Determination of plasma moxifloxacin in pulmonary tuberculosis patients: Significantly lower plasma concentrations of MFX, RMP and INH observed in tuberculosis patients who remained culture positive at two months than those who were culture negative suggest that drug levels are one of the key determinants in achieving early culture negativity.

•  Pharmacokinetics of second-line anti-tuberculosis drugs in children with multidrug-resistant tuberculosis in India: This study generated pharmacokinetic data for the first time in MDR-TB children in India. Majority of the children had therapeutic drug level indicating the adequacy of drug dosages.

Research Scholars:

Ph.D. student and Post Doctoral Fellow are carrying out their research in this laboratory with ICMR Fellowships

The laboratory has also been imparting observational training and internships to undergraduate and postgraduate students from different universities. We also guide post graduate students for their final year projects.