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KMID : 1146920220520040489
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Journal of Pharmaceutical Investigation
2022 Volume.52 No. 4 p.489 ~ p.499
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Early pharmacokinetic evaluation of anti-tubercular treatment as a good indicator of treatment success in pulmonary tuberculosis patients on a retreatment regimen
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Mohan Anant
Bhatnagar Anuj
Gupta Tarang
Ujjalkumar Das
Kanswal Sunita
Velpandian Thirumurthy
Guleria Randeep
Singh Urvashi B.
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Abstract
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Purpose: Patients with pulmonary tuberculosis (PTB) who fail therapy or develop a relapse are initiated on a retreatment regimen. These patients are at high risk for adverse outcomes. This study aimed to assess the relationship between plasma levels of anti-tubercular drugs and therapy outcome in patients on retreatment.
Methods: Pharmacokinetics of retreatment regimen drugs [isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA), ethambutol (EMB), and streptomycin (STM)] were compared between cured and not-cured patients using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in 134 patients with PTB on a retreatment regimen.
Results: Of 134 patients, 108 were cured, 17 developed multi-drug resistant TB (MDR-TB), and 9 remained smear-positive after completion of the retreatment (8 months). Two-hour plasma levels (C2hr) at Day 0 were lower in ‘not cured’ subjects than ‘cured’ subjects and reflected the drug levels achieved later in the duration of retreatment. Notably, in the 26 ‘not cured’ subjects, C2hr plasma levels after the first dose at Day 0 were significantly low (INH: 0.86 vs. 2.94 mg/L, p?≤?0.002, RIF: 0.56 vs. 2.55 mg/L, p?≤?0.003, PZA: 1.85 vs. 26.58 mg/L, p?≤?0.001 and EMB: 0.72 vs. 1.53 mg/L, p?≤?0.010).
Conclusion: Therapeutic failure in patients with PTB on a retreatment regimen is associated with lower plasma drug levels. Therapeutic drug monitoring would prove useful for obtaining a favorable clinical outcome. C2hr levels on Day 0 reflected drug levels achieved later and could be a good predictor of patient outcome.
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KEYWORD
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Therapeutic drug monitoring, Anti-tubercular therapy, Retreatment regimen, Pharmacokinetics
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