Skip to main content
SpringerLink
Log in

Clinical Pharmacokinetics and Pharmacodynamics of Rifampicin in Human Tuberculosis

  • Review Article
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Abstract

The introduction of rifampicin (rifampin) into tuberculosis (TB) treatment five decades ago was critical for shortening the treatment duration for patients with pulmonary TB to 6 months when combined with pyrazinamide in the first 2 months. Resistance or hypersensitivity to rifampicin effectively condemns a patient to prolonged, less effective, more toxic, and expensive regimens. Because of cost and fears of toxicity, rifampicin was introduced at an oral daily dose of 600 mg (8–12 mg/kg body weight). At this dose, clinical trials in 1970s found cure rates of ≥ 95% and relapse rates of < 5%. However, recent papers report lower cure rates that might be the consequence of increased emergence of resistance. Several lines of evidence suggest that higher rifampicin doses, if tolerated and safe, could shorten treatment duration even further. We conducted a narrative review of rifampicin pharmacokinetics and pharmacodynamics in adults across a range of doses and highlight variables that influence its pharmacokinetics/pharmacodynamics. Rifampicin exposure has considerable inter- and intra-individual variability that could be reduced by administration during fasting. Several factors including malnutrition, HIV infection, diabetes mellitus, dose size, pharmacogenetic polymorphisms, hepatic cirrhosis, and substandard medicinal products alter rifampicin exposure and/or efficacy. Renal impairment has no influence on rifampicin pharmacokinetics when dosed at 600 mg. Rifampicin maximum (peak) concentration (Cmax) > 8.2 μg/mL is an independent predictor of sterilizing activity and therapeutic drug monitoring at 2, 4, and 6 h post-dose may aid in optimizing dosing to achieve the recommended rifampicin concentration of ≥ 8 µg/mL. A higher rifampicin Cmax is required for severe forms TB such as TB meningitis, with Cmax ≥ 22 μg/mL and area under the concentration–time curve (AUC) from time zero to 6 h (AUC6) ≥ 70 μg·h/mL associated with reduced mortality. More studies are needed to confirm whether doses achieving exposures higher than the current standard dosage could translate into faster sputum conversion, higher cure rates, lower relapse rates, and less mortality. It is encouraging that daily rifampicin doses up to 35 mg/kg were found to be safe and well-tolerated over a period of 12 weeks. High-dose rifampicin should thus be considered in future studies when constructing potentially shorter regimens. The studies should be adequately powered to determine treatment outcomes and should include surrogate markers of efficacy such as Cmax/MIC (minimum inhibitory concentration) and AUC/MIC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Petersen E, Blumberg L, Wilson ME, Zumla A. Ending the global tuberculosis epidemic by 2030—the Moscow Declaration and achieving a major translational change in delivery of TB healthcare. Int J Infect Dis. 2017;65:156–8.

    Article  PubMed  Google Scholar 

  2. WHO. Global tuberculosis report 2017. Geneva: WHO Press; 2017.

    Google Scholar 

  3. Nahid P, Dorman SE, Alipanah N, et al. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America clinical practice guidelines: treatment of drug-susceptible tuberculosis. Clin Infect Dis. 2016;63(7):e147–95.

    Article  PubMed  PubMed Central  Google Scholar 

  4. WHO. Guidelines for treatment of drug-susceptible tuberculosis and patient care (2017 update). Geneva: WHO; 2018.

    Google Scholar 

  5. Ruslami R, Ganiem AR, Dian S, et al. Intensified regimen containing rifampicin and moxifloxacin for tuberculous meningitis: an open-label, randomised controlled phase 2 trial. Lancet Infect Dis. 2013;13(1):27–35.

    Article  PubMed  Google Scholar 

  6. Te Brake L, Dian S, Ganiem AR, et al. Pharmacokinetic/pharmacodynamic analysis of an intensified regimen containing rifampicin and moxifloxacin for tuberculous meningitis. Int J Antimicrob Agents. 2015;45:496–503.

    Article  CAS  Google Scholar 

  7. Sensi P. History of the development of rifampin. Rev Infect Dis. 1983;5(Suppl 3):S402–6.

    Article  CAS  PubMed  Google Scholar 

  8. van Ingen J, Aarnoutse RE, Donald PR, et al. Why do we use 600 mg of rifampicin in tuberculosis treatment? Clin Infect Dis. 2011;52(9):e194–9.

    Article  PubMed  CAS  Google Scholar 

  9. Controlled clinical trial of four short-course (6-month) regimens of chemotherapy for treatment of pulmonary tuberculosis. Third report. East African-British Medical Research Councils. Lancet. 1974;2(7875):237–40.

  10. Controlled clinical trial of short-course (6-month) regimens of chemotherapy for treatment of pulmonary tuberculosis. Lancet. 1972;299(7760):1079–1085.

  11. Goutelle S, Bourguignon L, Maire PH, Van Guilder M, Conte JE, Jelliffe RW. Population modeling and Monte Carlo simulation study of the pharmacokinetics and antituberculosis pharmacodynamics of rifampin in lungs. Antimicrob Agents Chemother. 2009;53(7):2974–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Jayaram R, Gaonkar S, Kaur P, et al. Pharmacokinetics-pharmacodynamics of rifampin in an aerosol infection model of tuberculosis. Antimicrob Agents Chemother. 2003;47(7):2118–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Gumbo T, Louie A, Deziel MR, et al. Concentration-dependent mycobacterium tuberculosis killing and prevention of resistance by rifampin. Antimicrob Agents Chemother. 2007;51(11):3781–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sloan DJ, McCallum AD, Schipani A, et al. Genetic determinants of the pharmacokinetic variability of rifampin in malawian adults with pulmonary tuberculosis. Antimicrob Agents Chemother. 2017;61(7):e00210–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Jeanes CW, Jessamine AG, Eidus L. Treatment of chronic drug-resistant pulmonary tuberculosis with rifampin and ethambutol. Can Med Assoc J. 1972;106(8):884–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Boeree MJ, Diacon AH, Dawson R, et al. A dose-ranging trial to optimize the dose of rifampin in the treatment of tuberculosis. Am J Respir Crit Care Med. 2015;191(9):1058–65.

    Article  CAS  PubMed  Google Scholar 

  17. Curci G, Bergamini N, Delli Veneri F, Ninni A, Nitti V. Half-life of rifampicin after repeated administration of different doses in humans. Chemotherapy. 1972;17(6):373–81.

    Article  CAS  PubMed  Google Scholar 

  18. Nitti V. Antituberculosis activity of rifampin. Report of studies performed and in progress (1966–1971). Chest. 1972;61(6):589–98.

  19. Svensson RJ, Aarnoutse RE, Diacon AH, et al. A population pharmacokinetic model incorporating saturable pharmacokinetics and autoinduction for high rifampicin doses. Clin Pharmacol Ther. 2018;103(4):674–83.

    Article  CAS  PubMed  Google Scholar 

  20. Furesz S, Scotti R, Pallanza R, Mapelli E. Rifampicin: a new rifamycin. 3. Absorption, distribution, and elimination in man. Arzneimittelforschung. 1967;17(5):534–7.

  21. Verbist L, Gyselen A. Antituberculous activity of rifampin in vitro and in vivo and the concentrations attained in human blood. Am Rev Respir Dis. 1968;98(6):923–32.

    CAS  PubMed  Google Scholar 

  22. Acocella G, Pagani V, Marchetti M, Baroni GC, Nicolis FB. Kinetic studies on rifampicin. I. Serum concentration analysis in subjects treated with different oral doses over a period of two weeks. Chemotherapy. 1971;16(6):356–70.

  23. Garnham JC, Taylor T, Turner P, Chasseaud LF. Serum concentrations and bioavailability of rifampicin and isoniazid in combination. Br J Clin Pharmacol. 1976;3(5):897–902.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Dickinson JM, Mitchison DA, Lee SK, et al. Serum rifampicin concentration related to dose size and to the incidence of the “flu” syndrome during intermittent rifampicin administration. J Antimicrob Chemother. 1977;3(5):445–52.

    Article  CAS  PubMed  Google Scholar 

  25. Milstein M, Lecca L, Peloquin C, et al. Evaluation of high-dose rifampin in patients with new, smear-positive tuberculosis (HIRIF): study protocol for a randomized controlled trial. BMC Infect Dis. 2016;16(1):453.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Sirgel FA, Fourie PB, Donald PR, et al. The early bactericidal activities of rifampin and rifapentine in pulmonary tuberculosis. Am J Respir Crit Care Med. 2005;172(1):128–35.

    Article  PubMed  Google Scholar 

  27. Ruslami R, Nijland HMJ, Alisjahbana B, Parwati I, van Crevel R, Aarnoutse RE. Pharmacokinetics and tolerability of a higher rifampin dose versus the standard dose in pulmonary tuberculosis patients. Antimicrob Agents Chemother. 2007;51(7):2546–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Chirehwa MT, Rustomjee R, Mthiyane T, et al. Erratum for Chirehwa et al., Model-based evaluation of higher doses of rifampin using a semimechanistic model incorporating autoinduction and saturation of hepatic extraction. Antimicrob Agents Chemother. 2016;60(5):3262.

  29. Constans P, Saint-Paul M, Morin Y, Bonnaud G, Bariéty M. Rifampicin: initial study of plasma levels during prolonged treatment of pulmonary tuberculosis patients [in French]. Rev Tuberc Pneumol (Paris). 1968;32(8):991–1006.

    CAS  PubMed  Google Scholar 

  30. Verbist L. Rifampicin blood levels in man. Acta Tuberc Pneumol Belg. 1969;60(3):288–98.

    CAS  PubMed  Google Scholar 

  31. Mouton RP, Mattie H, Swart K, Kreukniet J, de Wael J. Blood levels of rifampicin, desacetylrifampicin and isoniazid during combined therapy. J Antimicrob Chemother. 1979;5(4):447–54.

    Article  CAS  PubMed  Google Scholar 

  32. Burman WJ, Gallicano K, Peloquin C. Comparative pharmacokinetics and pharmacodynamics of the rifamycin antibacterials. Clin Pharmacokinet. 2001;40(5):327–41.

    Article  CAS  PubMed  Google Scholar 

  33. Strolin Benedetti M, Dostert P. Induction and autoinduction properties of rifamycin derivatives: a review of animal and human studies. Environ Health Perspect. 1994;102(Suppl 9):101–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Smythe W, Khandelwal A, Merle C, et al. A semimechanistic pharmacokinetic-enzyme turnover model for rifampin autoinduction in adult tuberculosis patients. Antimicrob Agents Chemother. 2012;56(4):2091–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Clewe O, Goutelle S, Conte JE, Simonsson USH. A pharmacometric pulmonary model predicting the extent and rate of distribution from plasma to epithelial lining fluid and alveolar cells—using rifampicin as an example. Eur J Clin Pharmacol. 2015;71(3):313–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Graham Douglas J, McLeod M-J. Pharmacokinetic factors in the modern drug treatment of tuberculosis. Clin Pharmacokinet. 1999;37(2):127–46.

    Article  Google Scholar 

  37. Acocella G, Bonollo L, Garimoldi M, Mainardi M, Tenconi LT, Nicolis FB. Kinetics of rifampicin and isoniazid administered alone and in combination to normal subjects and patients with liver disease. Gut. 1972;13(1):47–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. McIlleron H, Wash P, Burger A, Norman J, Folb PI, Smith P. Determinants of rifampin, isoniazid, pyrazinamide, and ethambutol pharmacokinetics in a cohort of tuberculosis patients. Antimicrob Agents Chemother. 2006;50(4):1170–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Mcilleron H, Wash P, Burger A, Folb P, Smith P. Widespread distribution of a single drug rifampicin formulation of inferior bioavailability in South Africa. Int J Tuberc Lung Dis. 2002;6(4):356–61.

    CAS  PubMed  Google Scholar 

  40. Boman G, Ringberger VA. Binding of rifampicin by human plasma proteins. Eur J Clin Pharmacol. 1974;7(5):369–73.

    Article  CAS  PubMed  Google Scholar 

  41. Woo J, Cheung W, Chan R, Chan HS, Cheng A, Chan K. In vitro protein binding characteristics of isoniazid, rifampicin, and pyrazinamide to whole plasma, albumin, and alpha-1-acid glycoprotein. Clin Biochem. 1996;29(2):175–7.

    Article  CAS  PubMed  Google Scholar 

  42. Donald PR. Cerebrospinal fluid concentrations of antituberculosis agents in adults and children. Tuberculosis. 2010;90(5):279–92.

    Article  CAS  PubMed  Google Scholar 

  43. Ellard GA, Humphries MJ, Allen BW. Cerebrospinal fluid drug concentrations and the treatment of tuberculous meningitis. Am Rev Respir Dis. 1993;148(3):650–5.

    Article  CAS  PubMed  Google Scholar 

  44. D’Oliveira JJG. Cerebrospinal fluid concentrations of rifampin in meningeal tuberculosis. Am Rev Respir Dis. 1972;106(3):432–7.

    Article  PubMed  Google Scholar 

  45. Larbaoui D, Boulahbal F, Ait-Khaled A, Baghbagha D, Benseman H, Bensafar SA. Serum and cerebrospinal fluid levels of rifampicin (R AMP) [in French]. Arch Inst Pasteur Alger. 1972;50–51:171–81.

    PubMed  Google Scholar 

  46. Mikhail IA, Girgis NI, Bourgeois LA, Lissner CR. Cerebrospinal fluid and serum concentrations of rifampin in meningeal tuberculosis after intravenous administration. Chemioterapia. 1987;6(2 Suppl):309–10.

    CAS  PubMed  Google Scholar 

  47. Nau R, Prange HW, Menck S, Kolenda H, Visser K, Seydel JK. Penetration of rifampicin into the cerebrospinal fluid of adults with uninflamed meninges. J Antimicrob Chemother. 1992;29(6):719–24.

    Article  CAS  PubMed  Google Scholar 

  48. Yunivita V, Dian S, Ganiem AR, et al. Pharmacokinetics and safety/tolerability of higher oral and intravenous doses of rifampicin in adult tuberculous meningitis patients. Int J Antimicrob Agents. 2016;48(4):415–21.

    Article  CAS  PubMed  Google Scholar 

  49. Gurumurthy P, Rahman F, Narayana AS, Sarma GR. Salivary levels of isoniazid and rifampicin in tuberculous patients. Tubercle. 1990;71(1):29–33.

    Article  CAS  PubMed  Google Scholar 

  50. Shenje J, Ifeoma Adimora-Nweke F, Ross IL, et al. Poor penetration of antibiotics into pericardium in pericardial tuberculosis. EBioMedicine. 2015;2(11):1640–9.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Donald PR. The chemotherapy of tuberculous meningitis in children and adults. Tuberculosis. 2010;90(6):375–92.

    Article  CAS  PubMed  Google Scholar 

  52. Binda G, Domenichini E, Gottardi A, et al. Rifampicin, a general review. Arzneimittelforschung. 1971;21(12):1907–77.

    CAS  PubMed  Google Scholar 

  53. Conte JE, Golden JA, Kipps JE, Lin ET, Zurlinden E. Effect of sex and AIDS status on the plasma and intrapulmonary pharmacokinetics of rifampicin. Clin Pharmacokinet. 2004;43(6):395–404.

    Article  CAS  PubMed  Google Scholar 

  54. Siegler DI, Bryant M, Burley DM, Citron KM, Standen SM. Effect of meals on rifampicin absorption. Lancet. 1974;2(7874):197–8.

    Article  CAS  PubMed  Google Scholar 

  55. Polasa K, Krishnaswamy K. Effect of food on bioavailability of rifampicin. J Clin Pharmacol. 1983;23(10):433–7.

    Article  CAS  PubMed  Google Scholar 

  56. Zent C, Smith P. Study of the effect of concomitant food on the bioavailability of rifampicin, isoniazid and pyrazinamide. Tuber Lung Dis. 1995;76(2):109–13.

    Article  CAS  PubMed  Google Scholar 

  57. Peloquin CA, Namdar R, Singleton MD, Nix DE. Pharmacokinetics of rifampin under fasting conditions, with food, and with antacids. Chest. 1999;115(1):12–8.

    Article  CAS  PubMed  Google Scholar 

  58. Buniva G, Pagani V, Carozzi A. Bioavailability of rifampicin capsules. Int J Clin Pharmacol Ther Toxicol. 1983;21(8):404–9.

    CAS  PubMed  Google Scholar 

  59. Lin H-C, Yu M-C, Liu H-J, Bai K-J. Impact of food intake on the pharmacokinetics of first-line antituberculosis drugs in Taiwanese tuberculosis patients. J Formos Med Assoc. 2014;113(5):291–7.

    Article  CAS  PubMed  Google Scholar 

  60. Vello GP, Vittori G. Ricerche sull’assorbimento orale e sulla eliminaxione urinaria della rifampicina. Gaz Intern Med Chirurg. 1968;73:2799–804.

    Google Scholar 

  61. Purohit SD, Johri SC, Gupta PR, Mehta YR, Bhatnagar M. Ranitidine–rifampicin interaction. J Assoc Physicians India. 1992;40(5):308–10.

    CAS  PubMed  Google Scholar 

  62. Gengiah TN, Botha JH, Soowamber D, Naidoo K, Abdool Karim SS. Low rifampicin concentrations in tuberculosis patients with HIV infection. J Infect Dev Ctries. 2014;8(8):987–93.

    Article  CAS  PubMed  Google Scholar 

  63. McIlleron H, Rustomjee R, Vahedi M, et al. Reduced antituberculosis drug concentrations in HIV-infected patients who are men or have low weight: implications for international dosing guidelines. Antimicrob Agents Chemother. 2012;56(6):3232–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. van Crevel R, Alisjahbana B, de Lange WCM, et al. Low plasma concentrations of rifampicin in tuberculosis patients in Indonesia. Int J Tuberc Lung Dis. 2002;6(6):497–502.

    Article  PubMed  Google Scholar 

  65. te Brake LHM, Ruslami R, Later-Nijland H, et al. Exposure to total and protein-unbound rifampin is not affected by malnutrition in indonesian tuberculosis patients. Antimicrob Agents Chemother. 2015;59(6):3233–9.

    Article  CAS  Google Scholar 

  66. Weiner M, Peloquin C, Burman W, et al. Effects of tuberculosis, race, and human gene SLCO1B1 polymorphisms on rifampin concentrations. Antimicrob Agents Chemother. 2010;54(10):4192–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Chigutsa E, Visser ME, Swart EC, et al. The SLCO1B1 rs4149032 polymorphism is highly prevalent in South Africans and is associated with reduced rifampin concentrations: dosing implications. Antimicrob Agents Chemother. 2011;55(9):4122–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Polasa K, Murthy KJ, Krishnaswamy K. Rifampicin kinetics in undernutrition. Br J Clin Pharmacol. 1984;17(4):481–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Polasa K, Krishnaswamy K. Rifampicin (600 mg) kinetics in the undernourished. Indian J Med Res. 1986;83:175–8.

    CAS  PubMed  Google Scholar 

  70. Kimerling ME, Phillips P, Patterson P, Hall M, Robinson CA, Dunlap NE. Low serum antimycobacterial drug levels in non-HIV-infected tuberculosis patients. Chest. 1998;113(5):1178–83.

    Article  CAS  PubMed  Google Scholar 

  71. Berning SE, Huitt GA, Iseman MD, Peloquin CA. Malabsorption of antituberculosis medications by a patient with AIDS. N Engl J Med. 1992;327(25):1817–8.

    Article  CAS  PubMed  Google Scholar 

  72. Taylor B, Smith PJ. Does AIDS impair the absorption of antituberculosis agents? Int J Tuberc Lung Dis. 1998;2(8):670–5.

    CAS  PubMed  Google Scholar 

  73. Peloquin CA, Nitta AT, Burman WJ, et al. Low Antituberculosis drug concentrations in patients with AIDS. Ann Pharmacother. 1996;30(9):919–25.

    Article  CAS  PubMed  Google Scholar 

  74. Sahai J, Gallicano K, Swick L, et al. Reduced plasma concentrations of antituberculosis drugs in patients with HIV infection. Ann Intern Med. 1997;127(4):289–93.

    Article  CAS  PubMed  Google Scholar 

  75. Patel KB, Belmonte R, Crowe HM. Drug malabsorption and resistant tuberculosis in HIV-infected patients. N Engl J Med. 1995;332(5):336–7.

    Article  CAS  PubMed  Google Scholar 

  76. Peloquin CA, MacPhee AA, Berning SE. Malabsorption of antimycobacterial medications. N Engl J Med. 1993;329(15):1122–3.

    Article  CAS  PubMed  Google Scholar 

  77. Alsultan A, Peloquin CA. Therapeutic drug monitoring in the treatment of tuberculosis: an update. Drugs. 2014;74(8):839–54.

    Article  CAS  PubMed  Google Scholar 

  78. Choudhri SH, Hawken M, Gathua S, et al. Pharmacokinetics of antimycobacterial drugs in patients with tuberculosis, AIDS, and diarrhea. Clin Infect Dis. 1997;25(1):104–11.

    Article  CAS  PubMed  Google Scholar 

  79. Jaruratanasirikul S. The pharmacokinetics of oral rifampicin in AIDS patients. J Med Assoc Thai. 1998;81(1):25–8.

    CAS  PubMed  Google Scholar 

  80. Acocella G. A metabolic and kinetic study on the association rifampicin-isoniazid. Respiration. 1971;28(Suppl):1–6.

    Article  Google Scholar 

  81. Capelle P, Dhumeaux D, Mora M, Feldmann G, Berthelot P. Effect of rifampicin on liver function in man. Gut. 1972;13(5):366–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Bright-Thomas RJ, Gondker AR, Morris J, Ormerod LP. Drug-related hepatitis in patients treated with standard anti-tuberculosis chemotherapy over a 30-year period. Int J Tuberc Lung Dis. 2016;20(12):1621–4.

    Article  CAS  PubMed  Google Scholar 

  83. Kumar N, Kedarisetty CK, Kumar S, Khillan V, Sarin SK. Antitubercular therapy in patients with cirrhosis: challenges and options. World J Gastroenterol. 2014;20(19):5760.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Durand F, Jebrak G, Pessayre D, Fournier M, Bernuau J. Hepatotoxicity of antitubercular treatments. Rationale for monitoring liver status. Drug Saf. 1996;15(6):394–405.

  85. A controlled trial of 6 months’ chemotherapy in pulmonary tuberculosis. Final report: results during the 36 months after the end of chemotherapy and beyond. British Thoracic Society. Br J Dis Chest. 1984;78(4):330–6.

  86. Combs DL, O’Brien RJ, Geiter LJ. USPHS Tuberculosis Short-Course Chemotherapy Trial 21: effectiveness, toxicity, and acceptability. The report of final results. Ann Intern Med. 1990;112(6):397–406.

  87. Hong YP, Kim SC, Chang SC, Kim SJ, Jin BW, Park CD. Comparison of a daily and three intermittent retreatment regimens for pulmonary tuberculosis administered under programme conditions. Tubercle. 1988;69(4):241–53.

    Article  PubMed  Google Scholar 

  88. Mitchison DA, Nunn AJ. Influence of initial drug resistance on the response to short-course chemotherapy of pulmonary tuberculosis. Am Rev Respir Dis. 1986;133(3):423–30.

    CAS  PubMed  Google Scholar 

  89. Franke MF, Appleton SC, Mitnick CD, et al. Aggressive regimens for multidrug-resistant tuberculosis reduce recurrence. Clin Infect Dis. 2013;56(6):770–6.

    Article  CAS  PubMed  Google Scholar 

  90. Kenny MT, Strates B. Metabolism and pharmacokinetics of the antibiotic rifampin. Drug Metab Rev. 1981;12(1):159–218.

    Article  CAS  PubMed  Google Scholar 

  91. Ellard GA. Chemotherapy of tuberculosis for patients with renal impairment. Nephron. 1993;64(2):169–81.

    Article  CAS  PubMed  Google Scholar 

  92. Wang CS, Yang CJ, Chen HC, et al. Impact of type 2 diabetes on manifestations and treatment outcome of pulmonary tuberculosis. Epidemiol Infect. 2009;137(02):203.

    Article  CAS  PubMed  Google Scholar 

  93. Alisjahbana B, Sahiratmadja E, Nelwan EJ, et al. The effect of type 2 diabetes mellitus on the presentation and treatment response of pulmonary tuberculosis. Clin Infect Dis. 2007;45(4):428–35.

    Article  PubMed  Google Scholar 

  94. Ruslami R, Nijland HMJ, Adhiarta IGN, et al. Pharmacokinetics of antituberculosis drugs in pulmonary tuberculosis patients with type 2 diabetes. Antimicrob Agents Chemother. 2010;54(3):1068–74.

    Article  CAS  PubMed  Google Scholar 

  95. Nijland HMJ, Ruslami R, Stalenhoef JE, et al. Exposure to rifampicin is strongly reduced in patients with tuberculosis and type 2 diabetes. Clin Infect Dis. 2006;43(7):848–54.

    Article  CAS  PubMed  Google Scholar 

  96. Babalik A, Ulus IH, Bakirci N, et al. Plasma concentrations of isoniazid and rifampin are decreased in adult pulmonary tuberculosis patients with diabetes mellitus. Antimicrob Agents Chemother. 2013;57(11):5740–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Brunton LL, Knollmann BC, Hilal-Dandan R. Goodman & Gilman’s the pharmacological basis of therapeutics. 13th ed. New York: McGraw Hill Medical; 2018.

    Google Scholar 

  98. Donald PR, Maritz JS, Diacon AH. The pharmacokinetics and pharmacodynamics of rifampicin in adults and children in relation to the dosage recommended for children. Tuberculosis. 2011;91(3):196–207.

    Article  CAS  PubMed  Google Scholar 

  99. Hartmann G, Honikel KO, Knüsel F, Nüesch J. The specific inhibition of the DNA-directed RNA synthesis by rifamycin. Biochim Biophys Acta. 1967;145(3):843–4.

    Article  CAS  PubMed  Google Scholar 

  100. Boeree MJ, Heinrich N, Aarnoutse R, et al. High-dose rifampicin, moxifloxacin, and SQ109 for treating tuberculosis: a multi-arm, multi-stage randomised controlled trial. Lancet Infect Dis. 2017;17(1):39–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. McColl KE, Thompson GG, el Omar E, Moore MR, Park BK, Brodie MJ. Effect of rifampicin on haem and bilirubin metabolism in man. Br J Clin Pharmacol. 1987;23(5):553–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Verbist L, Rollier F. Pharmacological study of rifampicin after repeated high dosage during intermittent combined therapy. II. Bilirubin levels and other biochemical determinations. Respiration. 1971;28(Suppl):17–28.

  103. Long MW, Snider DE, Farer LSUS. Public Health Service Cooperative trial of three rifampin-isoniazid regimens in treatment of pulmonary tuberculosis. Am Rev Respir Dis. 1979;119(6):879–94.

    CAS  PubMed  Google Scholar 

  104. Grosset J, Leventis S. Adverse effects of rifampin. Rev Infect Dis. 1983;5(Suppl 3):S440–50.

    Article  CAS  PubMed  Google Scholar 

  105. Kaneko Y, Nagayama N, Kawabe Y, et al. Drug-induced hepatotoxicity caused by anti-tuberculosis drugs in tuberculosis patients complicated with chronic hepatitis. Kekkaku. 2008;83(1):13–9.

    PubMed  Google Scholar 

  106. Saha A, Shanthi FXM, Winston AB, et al. Prevalence of hepatotoxicity from antituberculosis therapy: a five-year experience from South India. J Prim Care Community Health. 2016;7(3):171–4.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Tostmann A, Boeree MJ, Aarnoutse RE, de Lange WCM, van der Ven AJAM, Dekhuijzen R. Antituberculosis drug-induced hepatotoxicity: concise up-to-date review. J Gastroenterol Hepatol. 2008;23(2):192–202.

    Article  CAS  PubMed  Google Scholar 

  108. Kim D-H, Choi YH, Kim HS, Yu JE, Koh Y-I. A case of serum sickness-like reaction and anaphylaxis-induced simultaneously by rifampin. Allergy Asthma Immunol Res. 2014;6(2):183.

    Article  PubMed  Google Scholar 

  109. De Vriese AS, Robbrecht DL, Vanholder RC, Vogelaers DP, Lameire NH. Rifampicin-associated acute renal failure: pathophysiologic, immunologic, and clinical features. Am J Kidney Dis. 1998;31(1):108–15.

    Article  PubMed  Google Scholar 

  110. Ardern-Jones MR, Friedmann PS. Skin manifestations of drug allergy. Br J Clin Pharmacol. 2011;71(5):672–83.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Ye Y-M, Hur G-Y, Kim S-H, et al. Drug-specific CD4 + T-cell immune responses are responsible for antituberculosis drug-induced maculopapular exanthema and drug reaction with eosinophilia and systemic symptoms syndrome. Br J Dermatol. 2017;176(2):378–86.

    Article  CAS  PubMed  Google Scholar 

  112. A controlled trial of daily and intermittent rifampicin plus ethambutol in the retreatment of patients with pulmonary tuberculosis: results up to 30 months. Tubercle. 1975;56(3):179–89.

  113. Eidus L, Hodgkin MM, Hsu AH, Schaefer O. Pharmacokinetic studies with an isoniazid slow-releasing matrix preparation. Am Rev Respir Dis. 1974;110(1):34–42.

    CAS  PubMed  Google Scholar 

  114. Ormerod LP, Skinner C, Wales J. Hepatotoxicity of antituberculosis drugs. Thorax. 1996;51(2):111–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Grumbach F, Canetti G, Le Lirzin M. Rifampicin in daily and intermittent treatment of experimental murine tuberculosis, with emphasis on late results. Tubercle. 1969;50(3):280–93.

    Article  CAS  PubMed  Google Scholar 

  116. Jindani A, Aber VR, Edwards EA, Mitchison DA. The early bactericidal activity of drugs in patients with pulmonary tuberculosis. Am Rev Respir Dis. 1980;121(6):939–49.

    CAS  PubMed  Google Scholar 

  117. Chan SL, Yew WW, Ma WK, et al. The early bactericidal activity of rifabutin measured by sputum viable counts in Hong Kong patients with pulmonary tuberculosis. Tuber Lung Dis. 1992;73(1):33–8.

    Article  CAS  PubMed  Google Scholar 

  118. Sirgel FA, Botha FJ, Parkin DP, et al. The early bactericidal activity of rifabutin in patients with pulmonary tuberculosis measured by sputum viable counts: a new method of drug assessment. J Antimicrob Chemother. 1993;32(6):867–75.

    Article  CAS  PubMed  Google Scholar 

  119. Diacon AH, Patientia RF, Venter A, et al. Early bactericidal activity of high-dose rifampin in patients with pulmonary tuberculosis evidenced by positive sputum smears. Antimicrob Agents Chemother. 2007;51(8):2994–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Kreis B, Pretet S, Birenbaum J, et al. Two three-month treatment regimens for pulmonary tuberculosis. Bull Int Union Tuberc. 1976;51(1):71–5.

    CAS  PubMed  Google Scholar 

  121. Ruslami R, Nijland H, Aarnoutse R, et al. Evaluation of high- versus standard-dose rifampin in indonesian patients with pulmonary tuberculosis. Antimicrob Agents Chemother. 2006;50(2):822–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Peloquin CA. Therapeutic drug monitoring: principles and applications in mycobacterial infections. Drug Ther. 1992;22:31–6.

    Google Scholar 

  123. Chigutsa E, Pasipanodya JG, Visser ME, et al. Impact of nonlinear interactions of pharmacokinetics and MICs on sputum bacillary kill rates as a marker of sterilizing effect in tuberculosis. Antimicrob Agents Chemother. 2015;59(1):38–45.

    Article  PubMed  CAS  Google Scholar 

  124. Visser ME, Grewal HM, Swart EC, et al. The effect of vitamin A and zinc supplementation on treatment outcomes in pulmonary tuberculosis: a randomized controlled trial. Am J Clin Nutr. 2011;93(1):93–100.

    Article  CAS  PubMed  Google Scholar 

  125. Almeida D, Nuermberger E, Tasneen R, et al. Paradoxical effect of isoniazid on the activity of rifampin-pyrazinamide combination in a mouse model of tuberculosis. Antimicrob Agents Chemother. 2009;53(10):4178–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Grosset J, Truffot-Pernot C, Lacroix C, Ji B. Antagonism between isoniazid and the combination pyrazinamide-rifampin against tuberculosis infection in mice. Antimicrob Agents Chemother. 1992;36(3):548–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Moling O, Mian P. The high mortality rate associated with tuberculous meningitis. Clin Infect Dis. 1995;20(5):1429–30.

    Article  CAS  PubMed  Google Scholar 

  128. Doğanay M, Bakir M, Dökmetaş I. Treatment of tuberculous meningitis in adults with a combination of isoniazid, rifampicin and streptomycin: a prospective study. Scand J Infect Dis. 1989;21(1):81–5.

    Article  PubMed  Google Scholar 

  129. Verdon R, Chevret S, Laissy JP, Wolff M. Tuberculous meningitis in adults: review of 48 cases. Clin Infect Dis. 1996;22(6):982–8.

    Article  CAS  PubMed  Google Scholar 

  130. Yechoor VK, Shandera WX, Rodriguez P, Cate TR. Tuberculous meningitis among adults with and without HIV infection. Experience in an urban public hospital. Arch Intern Med. 1996;156(15):1710–6.

  131. Heemskerk AD, Bang ND, Mai NTH, et al. Intensified antituberculosis therapy in adults with tuberculous meningitis. N Engl J Med. 2016;374(2):124–34.

    Article  CAS  PubMed  Google Scholar 

  132. Aarnoutse RE, Kibiki GS, Reither K, et al. Pharmacokinetics, tolerability, and bacteriological response of rifampin administered at 600, 900, and 1,200 milligrams daily in patients with pulmonary tuberculosis. Antimicrob Agents Chemother. 2017;61(11):e01054-17.

    Article  PubMed  PubMed Central  Google Scholar 

  133. 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. 2010;16(10):1546–53.

    Article  PubMed  PubMed Central  Google Scholar 

  134. Magis-Escurra C, van den Boogaard J, IJdema D, Boeree M, Aarnoutse R. Therapeutic drug monitoring in the treatment of tuberculosis patients. Pulm Pharmacol Ther. 2012;25(1):83–86.

  135. Holland DP, Hamilton CD, Weintrob AC, et al. Therapeutic drug monitoring of antimycobacterial drugs in patients with both tuberculosis and advanced human immunodeficiency virus infection. Pharmacotherapy. 2009;29(5):503–10.

    Article  CAS  PubMed  Google Scholar 

  136. Burhan E, Ruesen C, Ruslami R, et al. Isoniazid, rifampin, and pyrazinamide plasma concentrations in relation to treatment response in indonesian pulmonary tuberculosis patients. Antimicrob Agents Chemother. 2013;57(8):3614–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Pasipanodya JG, McIlleron H, Burger A, Wash PA, Smith P, Gumbo T. Serum drug concentrations predictive of pulmonary tuberculosis outcomes. J Infect Dis. 2013;208(9):1464–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Magis-Escurra C, Later-Nijland HMJ, Alffenaar JWC, et al. Population pharmacokinetics and limited sampling strategy for first-line tuberculosis drugs and moxifloxacin. Int J Antimicrob Agents. 2014;44(3):229–34.

    Article  CAS  PubMed  Google Scholar 

  139. Sturkenboom MGG, Mulder LW, de Jager A, et al. Pharmacokinetic modeling and optimal sampling strategies for therapeutic drug monitoring of rifampin in patients with tuberculosis. Antimicrob Agents Chemother. 2015;59(8):4907–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Srivastava S, Gumbo T. Integrating drug concentrations and minimum inhibitory concentrations with Bayesian-dose optimisation for multidrug-resistant tuberculosis. Eur Respir J. 2014;43(1):312–3.

    Article  PubMed  Google Scholar 

  141. Vu DH, Alffenaar JWC, Edelbroek PM, Brouwers JRBJ, Uges DRA. Dried blood spots: a new tool for tuberculosis treatment optimization. Curr Pharm Des. 2011;17(27):2931–9.

    Article  CAS  PubMed  Google Scholar 

  142. Harahap Y, Alkindy F, Ashiila G, R R. Analysis of rifampicin in dried blood spot of tuberculosis patients for therapeutic drug monitoring using high performance liquid chromatography. J Young Pharm. 2018;10(1):48–51.

  143. Vu DH, Koster RA, Bolhuis MS, et al. Simultaneous determination of rifampicin, clarithromycin and their metabolites in dried blood spots using LC–MS/MS. Talanta. 2014;121:9–17.

    Article  CAS  PubMed  Google Scholar 

  144. Verbist L. Pharmacological study of rifampicin after repeated high dosage during intermittent combined therapy. I. Variation of the rifampicin serum levels (947 determinations). Respiration. 1971;28(Suppl):7–16.

  145. Boman G. Serum concentration and half-life of rifampicin after simultaneous oral administration of aminosalicylic acid or isoniazid. Eur J Clin Pharmacol. 1974;7(3):217–25.

    Article  CAS  PubMed  Google Scholar 

  146. Bhatia RS, Uppal R, Malhi R, Behera D, Jindal SK. Drug interaction between rifampicin and cotrimoxazole in patients with tuberculosis. Hum Exp Toxicol. 1991;10(6):419–21.

    Article  CAS  PubMed  Google Scholar 

  147. Acocella G, Luisetti M, Grassi GG, Peona V, Pozzi E, Grassi C. Bioavailability of isoniazid, rifampicin and pyrazinamide (in free combination or fixed-triple formulation) in intermittent antituberculous chemotherapy. Monaldi Arch Chest Dis. 1993;48(3):205–9.

    CAS  PubMed  Google Scholar 

  148. Peloquin CA, Jaresko GS, Yong CL, Keung AC, Bulpitt AE, Jelliffe RW. Population pharmacokinetic modeling of isoniazid, rifampin, and pyrazinamide. Antimicrob Agents Chemother. 1997;41(12):2670–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Zwolska Z, Niemirowska-Mikulska H, Augustynowicz-Kopec E, et al. Bioavailability of rifampicin, isoniazid and pyrazinamide from fixed-dose combination capsules. Int J Tuberc Lung Dis. 1998;2(10):824–30.

    CAS  PubMed  Google Scholar 

  150. Gurumurthy P, Ramachandran G, Vijayalakshmi S, et al. Bioavailability of rifampicin, isoniazid and pyrazinamide in a triple drug formulation: comparison of plasma and urine kinetics. Int J Tuberc Lung Dis. 1999;3(2):119–25.

    CAS  PubMed  Google Scholar 

  151. Pargal A, Rani S. Non-linear pharmacokinetics of rifampicin in healthy Asian Indian volunteers. Int J Tuberc Lung Dis. 2001;5(1):70–9.

    CAS  PubMed  Google Scholar 

  152. Prakash J, Velpandian T, Pande JN, Gupta SK. Serum rifampicin levels in patients with tuberculosis: effect of P-glycoprotein and CYP3A4 blockers on its absorption. Clin Drug Investig. 2003;23(7):463–72.

    Article  CAS  PubMed  Google Scholar 

  153. Agrawal S, Singh I, Kaur KJ, Bhade SR, Kaul CL, Panchagnula R. Comparative bioavailability of rifampicin, isoniazid and pyrazinamide from a four drug fixed dose combination with separate formulations at the same dose levels. Int J Pharm. 2004;276(1–2):41–9.

    Article  CAS  PubMed  Google Scholar 

  154. Gurumurthy P, Ramachandran G, Hemanth Kumar AK, et al. Decreased bioavailability of rifampin and other antituberculosis drugs in patients with advanced human immunodeficiency virus disease. Antimicrob Agents Chemother. 2004;48(11):4473–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. van Crevel R, Nelwan RH, Borst F, et al. Bioavailability of rifampicin in Indonesian subjects: a comparison of different local drug manufacturers. Int J Tuberc Lung Dis. 2004;8(4):500–3.

    PubMed  Google Scholar 

  156. Perlman DC, Segal Y, Rosenkranz S, et al. The clinical pharmacokinetics of rifampin and ethambutol in HIV-infected persons with tuberculosis. Clin Infect Dis. 2005;41(11):1638–47.

    Article  CAS  PubMed  Google Scholar 

  157. Tappero JW, Bradford WZ, Agerton TB, et al. Serum concentrations of antimycobacterial drugs in patients with pulmonary tuberculosis in Botswana. Clin Infect Dis. 2005;41(4):461–9.

    Article  CAS  PubMed  Google Scholar 

  158. Pinheiro VGF, Ramos LMA, Monteiro HSA, et al. Intestinal permeability and malabsorption of rifampin and isoniazid in active pulmonary tuberculosis. Braz J Infect Dis. 2006;10(6):374–9.

    Article  PubMed  Google Scholar 

  159. Weiner M, Burman W, Luo C-C, et al. Effects of rifampin and multidrug resistance gene polymorphism on concentrations of moxifloxacin. Antimicrob Agents Chemother. 2007;51(8):2861–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Um S-W, Lee SW, Kwon SY, et al. Low serum concentrations of anti-tuberculosis drugs and determinants of their serum levels. Int J Tuberc Lung Dis. 2007;11(9):972–8.

    PubMed  Google Scholar 

  161. McIlleron H, Norman J, Kanyok TP, Fourie PB, Horton J, Smith PJ. Elevated gatifloxacin and reduced rifampicin concentrations in a single-dose interaction study amongst healthy volunteers. J Antimicrob Chemother. 2007;60(6):1398–401.

    Article  CAS  PubMed  Google Scholar 

  162. Medellín-Garibay SE, Milán-Segovia R del C, Magaña-Aquino M, Portales-Pérez DP, Romano-Moreno S. Pharmacokinetics of rifampicin in Mexican patients with tuberculosis and healthy volunteers. J Pharm Pharmacol. 2014;66(10):1421–1428.

  163. Bhatt NB, Barau C, Amin A, et al. Pharmacokinetics of rifampin and isoniazid in tuberculosis-HIV-coinfected patients receiving nevirapine- or efavirenz-based antiretroviral treatment. Antimicrob Agents Chemother. 2014;58(6):3182–90.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  164. Kwara A, Cao L, Yang H, et al. Factors associated with variability in rifampin plasma pharmacokinetics and the relationship between rifampin concentrations and induction of efavirenz clearance. Pharmacother J Hum Pharmacol Drug Ther. 2014;34(3):265–71.

    Article  CAS  Google Scholar 

  165. Heinrich N, Dawson R, du Bois J, et al. Early phase evaluation of SQ109 alone and in combination with rifampicin in pulmonary TB patients. J Antimicrob Chemother. 2015;70(5):1558–66.

    Article  CAS  PubMed  Google Scholar 

  166. van Oosterhout JJ, Dzinjalamala FK, Dimba A, et al. Pharmacokinetics of antituberculosis drugs in HIV-positive and HIV-negative adults in Malawi. Antimicrob Agents Chemother. 2015;59(10):6175–80.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  167. Hemanth Kumar AK, Narendran G, Kumar RS, et al. RMP exposure is lower in HIV-infected TB patients receiving intermittent than daily anti-tuberculosis treatment. Int J Tuberc Lung Dis. 2015;19(7):805–7.

    Article  CAS  PubMed  Google Scholar 

  168. Hemanth Kumar AK, Kannan T, Chandrasekaran V, et al. Pharmacokinetics of thrice-weekly rifampicin, isoniazid and pyrazinamide in adult tuberculosis patients in India. Int J Tuberc Lung Dis. 2016;20(9):1236–41.

    Article  CAS  PubMed  Google Scholar 

  169. Saktiawati AMI, Sturkenboom MGG, Stienstra Y, et al. Impact of food on the pharmacokinetics of first-line anti-TB drugs in treatment-naive TB patients: a randomized cross-over trial. J Antimicrob Chemother. 2016;71(3):703–10.

    Article  CAS  PubMed  Google Scholar 

  170. Peloquin CA, Velásquez GE, Lecca L, et al. Pharmacokinetic evidence from the HIRIF trial to support increased doses of rifampin for tuberculosis. Antimicrob Agents Chemother. 2017;61(8):e00038-17.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 241, Cape Town, 8000, South Africa

    Ahmed Aliyu Abulfathi, Eric H. Decloedt & Helmuth Reuter

  2. Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands

    Elin M. Svensson

  3. Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden

    Elin M. Svensson

  4. Task Applied Science, Bellville, South Africa

    Andreas H. Diacon

  5. Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa

    Andreas H. Diacon

  6. Paediatrics and Child Health and Desmond Tutu TB Centre, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa

    Peter Donald

Authors
  1. Ahmed Aliyu Abulfathi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eric H. Decloedt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elin M. Svensson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andreas H. Diacon
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Peter Donald
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Helmuth Reuter
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ahmed Aliyu Abulfathi.

Ethics declarations

Conflict of interest

Ahmed A. Abulfathi has no conflict of interest to declare. Eric H. Decloedt has no conflict of interest to declare. Elin M. Svensson has no conflict of interest to declare. Andreas H. Diacon has no conflict of interest to declare. Peter Donald has no conflict of interest to declare. Helmuth Reuter has no conflict of interest to declare.

Funding

No funding was received for preparation of this manuscript.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abulfathi, A.A., Decloedt, E.H., Svensson, E.M. et al. Clinical Pharmacokinetics and Pharmacodynamics of Rifampicin in Human Tuberculosis. Clin Pharmacokinet 58, 1103–1129 (2019). https://doi.org/10.1007/s40262-019-00764-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40262-019-00764-2

Search

Navigation