Therapeutic Drug Monitoring of Isoniazid Among Newly Diagnosed Pulmonary Tuberculosis Patients

Abstract

Introduction: Tuberculosis has a higher incidence in lower income countries. Positive treatment outcomes may be fewer due to comorbidities like diabetes mellitus and immunosuppressive illnesses. The Global Tuberculosis Network working under the umbrella of World Health Organization has composed different committees. The TB Pharmacology Committee has given the concept of precision medicine and treatment based on drug susceptibility testing. Achievement of optimum plasma levels of anti-tuberculous drugs by therapeutic drug monitoring (TDM) is imperative and being emphasized to achieve a TB cure. Aims and Objectives: To determine the levels of INH in low responders to ATT have lower plasma levels of Isoniazid. Place and Duration of study: University of Health Sciences and Gulab Devi Chest Hospital, Lahore, for 1 year from August 2017- July 2018. Material and Methods: A first dose therapeutic drug monitoring (TDM) of isoniazid (INH) was planned in 25 newly enrolled sputum positive tuberculous patients at Gulab-Devi Hospital. The work was approved by Ethical Review Committee. Fixed dose combination (FDC) of anti-tuberculous drugs was given under direct observation and blood samples were withdrawn at two hours (C2h) and six hours (C6h) on days one, 14 and 56th of drug therapy. Samples of sputum for acid fast bacilli (AFB) were also taken during blood sampling. Method development and validation of isoniazid estimation by high-performance liquid chromatography was carried out. Plasma INH concentration in test samples was measured with Shimadzu Chromatographic System, Japan. Data was entered and analyzed using SPSS version 20. A p value ? 0.05 was taken as statistically significant. Results: Among 25 patients enrolled to the current study, the mean plasma levels of isoniazid were 1.29±0.79 µg / ml and 0.56±0.43 µg / ml at two hours and six hours respectively throughout the research duration. Most of the patients had lesser plasma INH levels than the target ranges (< 3µg / ml). Sputum for acid fast bacilli was found 100% positive on day one and 14 however sputum conversion was 56% after four weeks drug therapy. Conclusion: An early TDM monitoring has revealed low plasma INH concentration. Correction of dose to achieve expected plasma INH level will have promising effect on sputum culture conversion. It will minimize the total statewide burden of slow responders and tuberculosis resistant cases.