Therapeutic Drug Monitoring of Isoniazid Among Newly Diagnosed Pulmonary Tuberculosis Patients


  • Talha Laique Department of Pharmacology, Lahore Medical & Dental College, Lahore,
  • Navida Manzoor Department of Pharmacology, Rashid Latif Medical College, Lahore.
  • Qura-tul-ain Department of Pharmacology, Pak Red Cresent Medical College Dina Nath.
  • Sidra Mushtaq Department of Pharmacology, Independent Medical College Faisalabad.
  • Faiza Khan Department of Pharmacology, Pak Red Cresent Medical College Dina Nath.
  • Naseem Saud Department of Pharmacology, Superior University Lahore.



Therapeutic drug monitoring (TDM), isoniazid, HPLC


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 Fixed dose combination (FDC) of anti-tuberculous drugs was given under direct observation and blood samples were withdrawn at two hours (C2h) and six hours (C6h) on days one, 14 and 56th of drug therapy.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.


Ette EI, William PJ. Population Pharmacokinetics,I: background concepts, and models. Ann Pharmacother 2004; 38: 1702-6. Doi: 10.1345/aph.1D374

Khalid N, Ahmad F, Qureshi F M. Association amid the comorbidity of diabetes mellitus in patients of active tuberculosis in Pakistan: A matched case control study. Pakistan Journal of Medical Sciences. 2021; 37(3):816-820.

Alffenaar J-WC, Gumbo T, Dooley KE, Peloquin CA, McIlleron H, Zagorski A. et al. Integrating pharmacokinetics and pharmacodynamics in

operational research to end tuberculosis. Clinical Infectious Diseases. 2020; 70 (8): 1774-80.

Alamgir M, Sajjad M, Baig M S, Noori M Y. Mutational Frequencies in Mycobacterial rpoB gene using GeneXpert/MTB Rif assay in rifampicin resistant patients at a tertiary care setting in Urban Sindh, Pakistan: Analysis from a five-year period. Pakistan Journal of Medical Sciences . 2021; 37(4):1151-1154.


Global tuberculosis report 2021. Geneva: World Health Organization; 2021. Licence: CC BY-NC- SA 3.0 IGO.

Lei Q, Wang H, Zhao Y, Dang L, Zhu C, Lv X, Wang H, Zhou J. Determinants of serum concentration of first-line anti-tuberculosis drugs from China. Medicine (Baltimore). 2019 Oct;98(41):e17523.doi:10.1097/MD.0000000000017 523. PMID: 31593125; PMCID: PMC6799623.

van den Elsen SHJ, Oostenbrink LM, Heysell SK, Hira D, Touw DJ, Akkerman OW, Bolhuis MS, Alffenaar JC. Systematic review of salivary versus blood concentrations of antituberculosis drugs and their potential for salivary therapeutic drug monitoring. Therapeutic drug monitoring.2018; 40:17-3

Antunes MV, Linden R Paula Schaiquevich P. (2021) Therapeutic drug monitoring in developing nations: assessing the current state of affairs in South America., Expert Opinion on Drug Metabolism & Toxicology, 2021; 17:3, 251-254. DOI: 10.1080/17425255.2021.1859478.

Heysell SK, Moore JL, Keller SJ, Houpt ER. Therapeutic drug monitoring for slow response to tuberculosis treatment in a state control program, Virginia, USA. Emerg. Infect Dis.2011; 16(10):1546-1553. doi:10.3201/eid1610.100374

Schutz,H., 2011. Determining Optimal Sample Size, [online]. Available at :[Accessed 10 June 2016].

Laique T, Firdous A, Ashraf A, Ahmad A, Hussain H, and Rashid M. Development and validation of HPLC method for finding isoniazid plasma levels in TB patients with its quantification in FDC therapy. Pakistan Journal of Medical Health Sciences. 2019; 13(3): 674-678.

Laique T, Saud N, Firdous A, Ahmad A, Shujaat K, Babar A, Rashid M. Clinical outcomes in patients with multi drug resistant pulmonary tuberculosis after fixed dose combination therapy of anti- tuberculous drugs. Biomedica 2019; 35(4): 219-222.

Sadaf R, Munir T, Farrukh S, Abbasi S. Prevalence of latent tuberculosis infection in healthcare workers in tertiary care hospitals of Pakistan: Latent tuberculosis in healthcare workers. Pakistan Journal of Medical Health Sciences; 36(2):198-202.

Akhter N, Iqbal T, Jamil A, Akram M, Mehmood Tahir I, Munir N. Determination of arylamine N- acetyltransferase 2 acetylation genotype by PCR and

phenotyping using dapsone through high-pressure liquid chromatography assay: a gender wise study. Dose Response. 2019;17(2):. doi:10.1177/1559325819855537

Alffenaar J-WC, Akkerman OW, Kim HY, Tiberi S, Migliori GB. Precision and personalized medicine and anti-TB treatment: Is TDM feasible for programmatic use? International Journal of Infectious Diseases. 2020; 925: 55-59.

Fahimi F, Tabarsi P, Kobarfard F, Bozorg BD, Goodarzi A, Dastan F, et al. Isoniazid, rifampicin and pyrazinamide plasma concentrations 2 and 6 h post dose in patients with pulmonary tuberculosis. International Journal oftuberculosis andlung disease. 2013; 1: 17 (12): 1602-1606.

Prahl JB, Johansen IS, Cohen AS, Frimodt-Møller N, Andersen ÅB. Clinical significance of 2 h plasma concentrations of first-line anti-tuberculosis drugs: a prospective observational study.Journal of Antimicrobial Chemotherapy. 2014; 69(10):2841-7.

Burhan E, Ruesen C, Ruslami R, Ginanjar A, Mangunnegoro H, Ascobat, P, et al. Isoniazid, rifampin, and pyrazinamide plasma concentrations in relation to treatment response in Indonesian pulmonary tuberculosis patients. Antimicrobial agents and chemotherapy..2013; 57(8):3614-3619.

Heysell SK, Moore JL, Staley D, Dodge D, Houpt ER. Early therapeutic drug monitoring for isoniazid and rifampin among diabetics with newly diagnosed tuberculosis in Virginia, USA. Tuberculosis research and treatment. 2013 Oct; 2013:1-6.

Acquah SEK, Quaye L, Walana W, Vicar EK, Osei YN, Amedor al. Trends in sputum smear conversion among smear-positive pulmonary tuberculosis patients. Journal of Medical and Biomedical Sciences. 2015; 4: 24-33.

Tahir, M., Sharma, S.K., Rohrberg, D.S., Gupta, D., Singh, U.B. and Sinha, P.K., . DOTS at a tertiary care center in northern India: successes, challenges and the next steps in tuberculosis control. Indian Journal of Medical Research. 2006; 5: 702-706.

Djouma FN, Noubom M, AteudjieuJ, Donfack H. Delay in sputum smear conversion and outcomes of smear-positive tuberculosis patients: a retrospective cohort study in Bafoussam, Cameroon.BMC infectious diseases. 2015; 15(1): 139-146.

Mota PC, Carvalho A, Valente I, Braga R, Duarte R. Predictors of delayed sputum smear and culture conversion among a Portuguese population with pulmonary tuberculosis. Revista Portuguesa de- neumologia (English Edition). 2012; 18(2): 72-79.

Lee HY, Chae KO, Lee CH, Choi SM, Lee J, Park YS, et al. Culture conversion rate at 2 months of treatment according to diagnostic methods among patients with culture-positive pulmonary tuberculosis. PloS. One.2014; 9(8): 103768.

Sari DK, Mega JY, Harahap J. Nutrition status related to clinical improvement in AFB-Positive pulmonary tuberculosis patients in Primary Health Centers in Medan, Indonesia. . Open Access

Macedonian Journal of Medical Sciences. 2019; 7(10): 1621-1627.

Khan MA, Bilal W, Asim H, Rahmat ZS, Essar MY, Ahmad S. MDR-TB in Pakistan: Challenges, efforts, and recommendations. Annals of Medicine and Surgery. 2022 Jul 1;79:104009.

Jamil B, Nair D, Thekkur P, Laeeq N, Adil A, Khogali M, Zachariah R, Dar Berger S, Satyanarayana S, Kumar AM, Bochner A. Feasibility, enablers and challenges of using timeliness metrics for household contact tracing and TB preventive therapy in Pakistan. Plos one. 2023 Dec 11;18(12)e0295580

R Perumal, K Naidoo, N Padayatchi. Clinical impact of plasma concentrations of first-line antituberculosis drugs. S Afr Med J. 2023 Mar 2; 113(3): 148–153. doi: 10.7196/ SAMJ.2023.v 113i3.16761




How to Cite

Talha Laique, Navida Manzoor, Qura-tul-ain, Sidra Mushtaq, Faiza Khan, Naseem Saud. Therapeutic Drug Monitoring of Isoniazid Among Newly Diagnosed Pulmonary Tuberculosis Patients. Proceedings S.Z.M.C [Internet]. 2024 Apr. 29 [cited 2024 Jun. 25];38(2):73-8. Available from: