World Health Organization. Consolidated operational guidelines on handbook tuberculosis. Geneva: World Health Organization; 2020. p. 132.

Google Scholar 

Khoshnood S, Goudarzi M, Taki E, Darbandi A, Kouhsari E, Heidary M, et al. Bedaquiline: current status and future perspectives. J Glob Antimicrob Resist. 2021;25:48–59. https://doi.org/10.1016/j.jgar.2021.02.017.

Article  CAS  PubMed  Google Scholar 

Stancil SL, Mirzayev F, Abdel-Rahman SM. Profiling pretomanid as a therapeutic option for tb infection: evidence to date. Drug Des Devel Ther. 2021;15:2815–30.

Article  PubMed  PubMed Central  Google Scholar 

Conradie F, Diacon AH, Ngubane N, Howell P, Everitt D, Crook AM, et al. Treatment of highly drug-resistant pulmonary tuberculosis. N Engl J Med. 2020;382(10):893–902.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sarathy JP, Dartois V. Caseum: a Niche for Mycobacterium tuberculosis drug-tolerant persisters. Clin Microbiol Rev. 2020;33(3):e00159-19.

Ernest JP, Strydom N, Wang Q, Zhang N, Nuermberger E, Dartois V, et al. Development of new tuberculosis drugs: translation to regimen composition for drug-sensitive and multidrug-resistant tuberculosis. Annu Rev Pharmacol Toxicol. 2021;61:495–516.

Article  CAS  PubMed  Google Scholar 

Ordonez AA, Wang H, Magombedze G, Ruiz- CA, Srivastava S, Chen A, et al. Heterogeneous drug exposures in pulmonary lesions. HHS Public Access. 2020;26(4):529–34.

CAS  Google Scholar 

Kjellsson MC, Via LE, Goh A, Weiner D, Low KM, Kern S, et al. Pharmacokinetic evaluation of the penetration of antituberculosis agents in rabbit pulmonary lesions. Antimicrob Agents Chemother. 2012;56(1):446–57.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Strydom N, Gupta SV, Fox WS, Via LE, Bang H, Lee M, et al. Tuberculosis drugs’ distribution and emergence of resistance in patient’s lung lesions: a mechanistic model and tool for regimen and dose optimization. PLoS Med. 2019;16(4):e1002773.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dooley KE, Rosenkranz SL, Conradie F, Moran L, Hafner R, von Groote-Bidlingmaier F, et al. QT effects of bedaquiline, delamanid, or both in patients with rifampicin-resistant tuberculosis: a phase 2, open-label, randomised, controlled trial. Lancet Infect Dis. 2021;21(7):975–83. https://doi.org/10.1016/S1473-3099(20)30770-2.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cohen K, Maartens G. A safety evaluation of bedaquiline for the treatment of multi-drug resistant tuberculosis. Expert Opin Drug Saf. 2019;18(10):875–82. https://doi.org/10.1080/14740338.2019.1648429.

Article  CAS  PubMed  Google Scholar 

Tanneau L, Karlsson MO, Rosenkranz SL, Cramer YS, Shenje J, Upton CM, et al. Assessing prolongation of the corrected QT interval with bedaquiline and delamanid coadministration to predict the cardiac safety of simplified dosing regimens. Clin Pharmacol Ther. 2022;112(4):873–81.

Article  CAS  PubMed  PubMed Central  Google Scholar 

US FDA, Center For Drug Evaluation and Research. Center for Drug Evaluation and Research Application Number: 211810Orig1s000: multi-discipline review. US FDA; 2016. pp. 1–264. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212862Orig1s000MultidisciplineR.pdf.

Jermain B, Hanafin PO, Cao Y, Lifschitz A, Lanusse C, Rao GG. Development of a minimal physiologically-based pharmacokinetic model to simulate lung exposure in humans following oral administration of Ivermectin for COVID-19 drug repurposing. J Pharm Sci. 2020;109(12):3574–8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Brown RP, Delp MD, Lindstedt SL, Rhomberg LR, Beliles RP. Physiological parameter values for physiologically based pharmacokinetic models. Toxicol Ind Health. 1997;13(4):407–84.

Article  CAS  PubMed  Google Scholar 

Ngwalero P, Brust JCM, van Beek SW, Wasserman S, Maartens G, Meintjes G, et al. Relationship between plasma and intracellular concentrations of bedaquiline and its m2 metabolite in South African patients with rifampin-resistant tuberculosis. Antimicrob Agents Chemother. 2021;65:11.

Article  Google Scholar 

Tanneau L, Svensson EM, Rossenu S, Karlsson MO. Exposure–safety analysis of QTc interval and transaminase levels following bedaquiline administration in patients with drug-resistant tuberculosis. CPT Pharmacometrics Syst Pharmacol. 2021;10(12):1538–49.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gobburu JVS, Tammara V, Lesko L, Jhee SS, Sramek JJ, Cutler NR, et al. Pharmacokinetic-pharmacodynamic modeling of rivastigmine, a cholinesterase inhibitor, in patients with Alzheimer’s disease. J Clin Pharmacol. 2001;41(10):1082–90.

Article  CAS  PubMed  Google Scholar 

Chen RY, Yu X, Smith B, Liu X, Gao J, Diacon AH, et al. Radiological and functional evidence of the bronchial spread of tuberculosis: an observational analysis. Lancet Microbe. 2021;2(10):e518–26. https://doi.org/10.1016/S2666-5247(21)00058-6.

Article  PubMed  PubMed Central  Google Scholar 

Mahmood I, Balian JD. The pharmacokinetic principles behind scaling from preclinical results to phase I protocols. Clin Pharmacokinet. 1999;36(1):1–11.

Article  CAS  PubMed  Google Scholar 

Irwin SM, Prideaux B, Lyon ER, Zimmerman MD, Brooks EJ, Schrupp CA, et al. Bedaquiline and pyrazinamide treatment responses are affected by pulmonary lesion heterogeneity in mycobacterium tuberculosis infected C3HeB/FeJ mice. ACS Infect Dis. 2016;2(4):251–67.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Prideaux B, Via LE, Zimmerman MD, Eum S, Sarathy J, O’Brien P, et al. The association between sterilizing activity and drug distribution into tuberculosis lesions. Nat Med. 2015;21(10):1223–7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rouan MC, Lounis N, Gevers T, Dillen L, Gilissen R, Raoof A, et al. Pharmacokinetics and pharmacodynamics of TMC207 and its N-desmethyl metabolite in a murine model of tuberculosis. Antimicrob Agents Chemother. 2012;56(3):1444–51.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ahmad Z, Peloquin CA, Singh RP, Derendorf H, Tyagi S, Ginsberg A, et al. PA-824 exhibits time-dependent activity in a murine model of tuberculosis. Antimicrob Agents Chemother. 2011;55(1):239–45.

Article  CAS  PubMed  Google Scholar 

Mota F, Ruiz-Bedoya C, Tucker E, De Jesus P, Flavahan K, Turner M, et al. Noninvasive assessment of intralesional antimicrobial concentration-time profiles in pulmonary and central nervous system tuberculosis using dynamic 18F-pretomanid positron emission tomography. Open Forum Infect Dis. 2021;8(Suppl 1):S789–90. https://doi.org/10.1093/ofid/ofab466.1603.

Article  PubMed Central  Google Scholar 

Ismail NA, Omar SV, Joseph L, Govender N, Blows L, Ismail F, et al. Defining bedaquiline susceptibility, resistance, cross-resistance and associated genetic determinants: a retrospective cohort study. EBioMedicine. 2018;28:136–42. https://doi.org/10.1016/j.ebiom.2018.01.005.

Article  PubMed  PubMed Central  Google Scholar 

van Heeswijk RPG, Dannemann B, Hoetelmans RMW. Bedaquiline: a review of human pharmacokinetics and drug-drug interactions. J Antimicrob Chemother. 2014;69(9):2310–8.

Article  PubMed  Google Scholar 

Diacon AH, Dawson R, Von Groote-Bidlingmaier F, Symons G, Venter A, Donald PR, et al. Bactericidal activity of pyrazinamide and clofazimine alone and in combinations with pretomanid and bedaquiline. Am J Respir Crit Care Med. 2015;191(8):943–53.

Article  CAS  PubMed  Google Scholar 

Chesov E, Chesov D, Maurer FP, Andres S, Utpatel C, Barilar I, et al. Emergence of bedaquiline resistance in a high tuberculosis burden country. Eur Respir J. 2022;59(3):1–10. https://doi.org/10.1183/13993003.00621-2021.

Article  CAS  Google Scholar 

Allué-Guardia A, Garcia-Vilanova A, Olmo-Fontánez AM, Peters J, Maselli DJ, Wang Y, et al. Host- and age-dependent transcriptional changes in Mycobacterium tuberculosis cell envelope biosynthesis genes after exposure to human alveolar lining fluid. Int J Mol Sci. 2022;23(2). https://www.mdpi.com/1422-0067/23/2/983

Drusano GL, Kim S, Almoslem M, Schmidt S, D’Argenio DZ, Myrick J, et al. The funnel: a screening technique for identifying optimal two-drug combination chemotherapy regimens. Antimicrob Agents Chemother. 2021;65:2.

Article  Google Scholar 

Jarugula P, Scott S, Ivaturi V, Noack A, Moffett BS, Bhutta A, et al. Understanding the role of pharmacometrics-based clinical decision support systems in pediatric patient management: a case study using Lyv software. J Clin Pharmacol. 2021;61(Suppl 1):S125–32.

CAS  PubMed  Google Scholar 

Hughes JH, Tong DMH, Lucas SS, Faldasz JD, Goswami S, Keizer RJ. Continuous learning in model-informed precision dosing: a case study in pediatric dosing of vancomycin. Clin Pharmacol Ther. 2021;109(1):233–42.

Article  CAS  PubMed  Google Scholar 

Humphries H, Almond L, Berg A, Gardner I, Hatley O, Pan X, et al. Development of physiologically-based pharmacokinetic models for standard of care and newer tuberculosis drugs. CPT Pharmacometrics Syst Pharmacol. 2021;10(11):1382–95.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cao Y, Jusko WJ. Applications of minimal physiologically-based pharmacokinetic models. J Pharmacokinet Pharmacodyn. 2012;39(6):711–23.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rowland M, Tozer TN. Clinical pharmacokinetics and pharmacodynamics: concepts and applications; 1980.

Shargel L, Wu-Pong S, Yu ABC. Chapter 10. physiologic drug distribution and protein binding. In: Applied biopharmaceutics and pharmacokinetics, 6e. New York: The McGraw-Hill Companies; 2012. http://accesspharmacy.mhmedical.com/content.aspx?aid=56603200.

Diacon AH, Dawson R, von Groote-Bidlingmaier F, Symons G, Venter A, Donald PR, et al. 14-day bactericidal activity of PA-824, bedaquiline, pyrazinamide, and moxifloxacin combinations: a randomised trial. Lancet. 2012;380(9846):986–93.

Article  CAS  PubMed  Google Scholar 

The global alliance for tb drug development. Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis (TMC207-CL001). 2017. https://clinicaltrials.gov/show/NCT01215110.