• Geetha Ramachandran, A K Hemanth Kumar, T Kannan, Balamugesh Thangakunam, Deepa Shankar, and Devasahayam J Christopher.
• Department of Biochemistry & Clinical Pharmacology, ICMR-National Institute for Research in Tuberculosis, Chennai, Tamil Nadu, India.
• Indian J Med Res. 2023 Feb 1; 157 (2&3): 211215211-215.

Background & ObjectivesThe National Tuberculosis (TB) Control Programme has transitioned from thrice-weekly to daily drug treatment regimens in India. This preliminary study was conceived to compare the pharmacokinetics of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) in TB patients being treated with daily and thrice weekly anti-TB treatment (ATT).MethodsThis prospective observational study was undertaken in 49 newly diagnosed adult TB patients receiving either daily ATT (n=22) or thrice-weekly ATT (n=27). Plasma RMP, INH and PZA were estimated by high-performance liquid chromatography.ResultsThe peak concentration (Cmax) of RMP was significantly higher (RMP: 8.5 μg/ml vs. 5.5 μg/ml; P=0.003) and Cmax of INH was significantly lower (INH: 4.8 μg/ml vs. 10.9 μg/ml; P<0.001) in case of daily dosing compared to thrice-weekly ATT. Cmax of drugs and doses was significantly correlated. A higher proportion of patients had subtherapeutic RMP Cmax (8.0 μg/ml) during thrice-weekly compared to daily ATT (78% vs. 36%; P=0.004). Multiple linear regression analysis showed that Cmax of RMP was significantly influenced by the dosing rhythm, pulmonary TB and Cmax of INH and PZA by the mg/kg doses.Interpretation & ConclusionsRMP concentrations were higher and INH concentrations were lower during daily ATT, suggesting that INH doses may need to be increased in case of a daily regimen. Larger studies are, however, required using higher INH doses when monitoring for adverse drug reactions and treatment outcomes.

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