A validated LC-MS/MS method for simultaneous quantification of antitubercular drugs in rat plasma and its application for a pharmacokinetic interaction study with Immusante®

Lakavalli Mohankumar Sharath Kumar Mohammed Mukhram Azeemuddin Krishna Chaitanya Routhu Keerthi Priya Uddagiri Venkanna Babu Sreedhara Ranganath Pai   

Open Access   

Published:  Mar 04, 2023

DOI: 10.7324/JAPS.2023.118956
Abstract

Tuberculosis is caused by Mycobacterium tuberculosis, and it is a contagious disease. Primary empiric treatment for tuberculosis comprises a four-drug regimen: Isoniazid, Rifampicin, Pyrazinamide, and Ethambutol. The disease and its treatment may pose undernutrition due to the increased metabolic load and decreased food intake. Immunomodulators and micronutrients are consumed by patients, worldwide, to counteract nutritional insufficiencies. Immusante® is a polyherbal formulation recommended as an immunomodulator in various immunocompromised states, including tuberculosis. This study aims to identify the pharmacokinetic interactions between the first-line antituberculosis (anti-TB) drugs, that is, AKT-4 tablets (a combination of isoniazid, rifampicin, pyrazinamide, and ethambutol), and Immusante®. We developed a method of sensitive liquid chromatography with tandem mass spectrometry for the simultaneous quantification of isoniazid, rifampicin, pyrazinamide, and ethambutol in rat plasma and validated it as per the European Medicines Agency guidelines. The method was used to quantify all four drugs in rat plasma treated with a combination of AKT-4 and Immusante®. No significant alterations in the values of various pharmacokinetic parameters such as Vd, t1/2, CL, tmax, Cmax, and AUC were observed, indicating that coadministration of Immusante® does not influence the pharmacokinetic profiles of the anti-TB drugs. Thus, Immusante® can be recommended as an adjuvant for its immunomodulatory activity in anti-TB drug therapy.


Keyword:      Isoniazid immusante pharmacokinetics LC-MS/ MS tuberculosis


Citation:

Sharath Kumar LMK, Azeemuddin MM, Routhu KC, Priya K, Babu UV, Pai SR. A validated LC-MS/MS method for simultaneous quantification of antitubercular drugs in rat plasma and its application for a pharmacokinetic interaction study with Immusante®. J Appl Pharm Sci, 2023. https://doi.org/10.7324/JAPS.2023.118956

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Reference

Agraz AV, Rafiq M, Guru B, Madan MN, Anturlikar SD, Azeemuddin MM, Manjula SN. Evaluation of immunomodulatory activity of Immusante® in zebrafish. J Appl Biol Biotechnol, 2021; 9(3):7-2.

Elgawish MS, Soltan MK, Sebaiy MM. An LC-MS/MS spectrometry method for the simultaneous determination of Rosuvastatin and irbesartan in rat plasma: insight into pharmacokinetic and drug-drug interaction studies. J Pharm Biomed Anal, 2019; 174:226-34.
https://doi.org/10.1016/j.jpba.2019.05.069

Firashathulla S, Inamdar MN, Rafiq M, Viswanatha GL, Sharath Kumar LM, Babu UV, Ramakrishnan S, Paramesh R. IM-133N-a useful herbal combination for eradicating disease-triggering pathogens in mice via immunotherapeutic mechanisms. J Pharmacopuncture, 2016; 19(1):21-7. doi: 10.3831/KPI.2016.19.003.
https://doi.org/10.3831/KPI.2016.19.003

International Transporter Consortium, Giacomini KM, Huang SM, Tweedie DJ, Benet LZ, Brouwer KL, Chu X, Dahlin A, Evers R, Fischer V, Hillgren KM, Hoffmaster KA, Ishikawa T, Keppler D, Kim RB, Lee CA, Niemi M, Polli JW, Sugiyama Y, Swaan PW, Ware JA, Wright SH, Yee SW, Zamek- Gliszczynski MJ, Zhang L. Membrane transporters in drug development. Nat Rev Drug Discov, 2010; 9(3):215-36; doi: 10.1038/nrd3028.
https://doi.org/10.1038/nrd3028

Jayanthi CR, Avinash HR, Sridhar S, Akhila K, Kumawat R. A randomized control study to evaluate the role of herbal immunomodulators in boosting the immunity and overall health of healthcare workers in COVID-19 wards: an exploratory, feedback clinical study. Asian J Pharm Clin Res, 2021; 14:138-42.
https://doi.org/10.22159/ajpcr.2021.v14i8.42035

Le Blaye O. The EMA guideline on bioanalytical method validation. EMA, London, UK, 2011.

Gangwar V, Garg A, Lomore K, Korla K, Bhat SS, Rao RP, Rafiq M, Kumawath R, Uddagiri BV, Kareenhalli VV. Immunomodulatory effects of a concoction of natural bioactive compounds-mechanistic insights. Biomedicines. 2021; 9(11):1522.
https://doi.org/10.3390/biomedicines9111522

Giacomini KM, Huang SM. Transporters in drug development and clinical pharmacology. Clin Pharmacol Ther, 2013; 94(1):3-9. doi: 10.1038/clpt.2013.86.
https://doi.org/10.1038/clpt.2013.86

Grobler L, Durao S, Van Der Merwe S M, Wessels J, Naude C E. Nutritional supplements for people being treated for active tuberculosis: a technical summary. S Afr Med J, 2016; 108(1):16-8.
https://doi.org/10.7196/SAMJ.2017.v108i1.12839

Long NP, Par S, Anh .H, Kim SJ, Kim HM, Yoon SJ, Lim J, & Kwon SW. Advances in liquid chromatography-mass spectrometry-based lipidomics: a look ahead. J Anal Test, 2020; 4:1-5.
https://doi.org/10.1007/s41664-020-00135-y

Marsot A, Ménard A, Dupouey J, Muziotti C, Guilhaumou R, Blin O. Population pharmacokinetics of rifampicin in adult patients with osteoarticular infections: interaction with fusidic acid. Br J Clin Pharmacol, 2017; 83(5):1039-47; doi: 10.1111/bcp.13178.
https://doi.org/10.1111/bcp.13178

Nishimura Y, Kurata N, Sakurai E, Yasuhara H. Inhibitory effect of antituberculosis drugs on human cytochrome P450-mediated activities. J Pharmacol Sci, 2004; 96(3):293-300.
https://doi.org/10.1254/jphs.FP0040296

Sachin BS, Monica P, Sharma SC, Satti NK, Tikoo MK, Tikoo AK. Pharmacokinetic interaction of some antitubercular drugs with caraway: implications in the enhancement of drug bioavailability. Hum Exp Toxicol, 2009; 28:175-84.
https://doi.org/10.1177/0960327108097431

Tasduq SA, Kaiser P, Sharma SC, Johri RK. Potentiation of isoniazid-induced liver toxicity by rifampicin in a combinational therapy of antitubercular drugs (rifampicin, isoniazid and pyrazinamide) in Wistar rats: a toxicity profile study. Hepatol Res, 2007; 37(10):845-53. doi: 10.1111/j.1872-034X.2007.00129.x.
https://doi.org/10.1111/j.1872-034X.2007.00129.x

Unissa AN, Selvakumar N, Narayanan S. Characterization of isoniazid-resistant mutant (S315R) of catalase-peroxidase, KatG, from Mycobacterium tuberculosis. Int J Med Sci Technol, 2011; 4(3):13-22.

Vavricka SR, Van Montfoort J, Ha HR, Meier PJ, Fattinger K. Interactions of rifamycin SV and rifampicin with organic anion uptake systems of human liver. Hepatology, 2002; 36(1):164-72. doi: 10.1053/ jhep.2002.34133.
https://doi.org/10.1053/jhep.2002.34133

Venkatesan K. Pharmacokinetic drug interactions with rifampicin. Clin Pharmacokinet, 1992; 22(1):47-65; doi: 10.2165/00003088- 199222010-00005. Zhang L, Zhao Y, Gao Y, Wu L, Gao R, Zhang Q, Wang Y, Wu C, Wu F, Gurcha SS, Veerapen N, Batt SM, Zhao W, Qin L, Yang X, Wang M, Zhu Y, Zhang B, Bi L, Zhang X, Yang H, Guddat LW, Xu W, Wang Q, Li J, Besra GS, Rao Z. Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol. Science, 2020; 368(6496):1211-9; doi: 10.1126/science.aba9102.
https://doi.org/10.1126/science.aba9102

Zhang Y, Shi W, Zhang W, Mitchison D. Microbiol Spectr, 2014; 2(4):1-2.
https://doi.org/10.1128/microbiolspec.MGM2-0023-2013

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