Pharmacokinetic Study of Bedaquiline Among Indian Mdr-TB Patients in Clinical Settings

Abstract

BACKGROUND: Bedaquiline, a novel drug was approved for the treatment of multidrug resistance tuberculosis (MDR-TB) by the US FDA in 2012. It is majorly caused because of the transmission of multi-resistant strain from diseased person to a healthy individual and by genetic factors. Safety, efficacy and bactericidal activity of Bedaquiline were reported in various studies, but the pharmacokinetic analysis of Bedaquiline in clinical settings was unclear. A simple and selective HPLC-UV method was developed to determine the concentration of Bedaquiline and applicable to report pharmacokinetic parameters. This study serves as evidence for the physicians regarding the pharmacokinetic data and managing drug therapy and for better patient outcomes in routine clinical practice.

METHODS: This study is conducted in newly diagnosed, smear-positive, MDR-TB patients who received Bedaquiline as per RNTCP guidelines. Plasma samples were collected after the Bedaquiline administration. The patient samples were analyzed by high-performance liquid chromatography equipped with a UV-Visible detector. The pharmacokinetic data were drawn by using software kinetic-2000, version 5.03.

RESULTS: From December 2018 to May 2019, a total of 58 patients with newly diagnosed, smear-positive, multidrug-resistant pulmonary tuberculosis administering Bedaquilline were included in this study. The observed Cmax was 2523.08 ng/mL, Tmax was reached at 4 hrs, AUC(0-24) was 21727.1 ng *hr/mL, AUMC (0-24) was 222953.8 ng *hr2/mL. Whereas the half-life of the drug was found at 7 .02 hrs and mean residence time (MRT) was found to be 10.25 hrs respectively.

CONCLUSION: Conclusively, pharmacokinetic parameters were evaluated and found to be within the desired limits. This method can be further used for the quantification of Bedaquiline in routine clinical practice.

Keywords: MDR-TB, RNTCP guidelines, Bedaquiline, HPLC, Pharmacokinetics and Clinical practice