Drugs

, Volume 62, Issue 15, pp 2169–2183 | Cite as

Therapeutic Drug Monitoring in the Treatment of Tuberculosis

Current Opinion

Abstract

Therapeutic drug monitoring (TDM) is a standard clinical technique used for many disease states, including many infectious diseases. As for these other conditions, the use of TDM in the setting of tuberculosis (TB) allows the clinician to make informed decisions regarding the timely adjustment of drug therapy. Such adjustments may not be required for otherwise healthy individuals who are responding to the standard, four-drug TB regimens. However, some patients are slow to respond to treatment, have drug-resistant TB, are at risk of drug-drug interactions or have concurrent disease states that significantly complicate the clinical situation. Such patients may benefit from TDM and early interventions may preclude the development of further drug resistance.

It is not possible to collect multiple blood samples in the clinical setting for logistical and financial reasons. Therefore, one typically is limited to one or two time points. When only one sample can be obtained, the 2-hour post-dose concentrations of isoniazid, rifampin, pyrazinamide and ethambutol are usually most informative. Unfortunately, low 2-hour values do not distinguish between delayed absorption (late peak, close to normal range) and malabsorption (low concentrations at all time points). A second sample, often collected at 6-hour post-dose, can differentiate between these two scenarios. The second time point can also provide some information about clearance and half-life, assuming that drug absorption was nearly completed by 2 hours. TDM requires that samples are promptly centrifuged, and that the serum is promptly harvested and frozen. Isoniazid and ethionamide, in particular, are not stable in human serum at room temperature. Rifampin is stable for more than 6 hours under these conditions.

During TB treatment, isoniazid causes the greatest early reduction in organisms and is considered to be one of the two most important TB drugs, along with rifampin. Although isoniazid is highly active against TB, low isoniazid concentrations were associated with poorer clinical and bacteriological outcomes in US Public Health Services (USPHS) TB Trial 22. Several earlier trials showed a clear dose-response for rifampin and pyrazinamide, so low concentrations for those two drugs also may correlate with poorer treatment outcomes. At least in USPHS TB Trial 22, the rifampin pharmacokinetic parameters were not predictive of the outcome variables. In contrast, low concentrations of unbound rifapentine may have been responsible, in part, for the worse-than-anticipated performance of this drug in clinical trials.

The ‘second-line’ TB drugs, including p-aminosalicylic acid, cycloserine and ethionamide, are relatively weak TB drugs. Under the best conditions, treatment with these drugs takes over 2 years, as opposed to 6 to 9 months with isoniazid- and rifampin-containing regimens. Therefore, TB centres such as National Jewish Medical and Research Center in Denver, CO, USA, measure serum concentrations of the ‘second-line’ TB drugs early in the course of treatment. That way, poor drug absorption can be dealt with in a timely manner. This helps to minimise the time that patients are sputum smear- and culture-positive with multidrug-resistant TB, and may prevent the need for even longer treatment durations.

Patients with HIV are at particular risk for drug-drug interactions. Because the published guidelines typically reflect interactions only between two drugs, these guidelines are of limited value when the patient is treated with three or more interacting drugs. Under such complicated circumstances, TDM often is the best available tool for sorting out these interactions and placing the patient the necessary doses that they require.

TDM is only one part of the care of patients with TB. In isolation, it is of limited value. However, combined with clinical and bacteriological data, it can be a decisive tool, allowing the clinician to successfully treat even the most complicated TB patients.

Keywords

Rifampicin Isoniazid Therapeutic Drug Monitoring Ethambutol Pyrazinamide 

Notes

Acknowledgements

The author has provided no information on sources of funding or on conflicts of interest directly relevant to the content of this review/study.

References

  1. 1.
    Peloquin CA, Ebert SC. Tuberculosis. In: DiPiro JT, Talbert RL, Yee GC, et al., editors. Pharmacotherapy: A pathophysiologic Approach. 4th ed. Stamford (CT): Appleton & Lange, 1999: 1717–36Google Scholar
  2. 2.
    American Thoracic Society. Targeted tuberculin skin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000; 161: S221–47Google Scholar
  3. 3.
    Verbist L. Mode of action of antituberculous drugs: I. Medikon 1974; 3: 11–23Google Scholar
  4. 4.
    Verbist L. Mode of action of antituberculous drugs: II. Medikon 1979; 3: 3–17Google Scholar
  5. 5.
    Winder FG. Mode of action of the antimycobacterial agents and associated aspects of the molecular biology of the mycobacteria. In: Rat-ledge C, Stanford J, editors. The Biology of Mycobacteria: Vol1. Physiology, Identification, and Classification. London: Academic Press, 1982: 353–438Google Scholar
  6. 6.
    Peloquin CA. Using therapeutic drug monitoring to dose the antimycobacterial drugs. Clin Chest Med 1997; 18: 79–87PubMedCrossRefGoogle Scholar
  7. 7.
    Heym B, Saint-Joanis B, Cole ST. The molecular basis of isoniazid resistance in Mycobacterium tuberculosis. Tuber Lung Dis 1999; 79: 267–71PubMedCrossRefGoogle Scholar
  8. 8.
    Somoskovi A, Parsons LM, Salfinger M. The molecular basis of resistance to isoniazid, rifampin, and pyrazinamide in Mycobacterium tuberculosis. Respir Res 2001; 2: 164–8PubMedCrossRefGoogle Scholar
  9. 9.
    Mitchison DA. Basic mechanisms of chemotherapy. Chest 1979; 76: 771–81PubMedGoogle Scholar
  10. 10.
    Fox W, Ellard GA, Mitchison DA. Studies on the treatment of tuberculosis undertaken by the British Medical Research Council Tuberculosis Units, 1946–1986, with relevant subsequent publications. Int JTuberc Lung Dis 1999; 3: S231–79Google Scholar
  11. 11.
    Mitchison DA. Role of individual drugs in the chemotherapy of tuberculosis. Int J Tuberc Lung Dis 2000; 4: 796–806PubMedGoogle Scholar
  12. 12.
    Hernández-Pando R, Jeyanthan M, Mengistu G, et al. Persistence of DNA from Mycobacterium tuberculosis in superficially normal lung tissue during latent infection. Lancet 2000; 356: 2133–7PubMedCrossRefGoogle Scholar
  13. 13.
    Bishai WR. Rekindling old controversy on elusive lair of latent tuberculosis. Lancet 2000; 356: 2113–4PubMedCrossRefGoogle Scholar
  14. 14.
    Flynn JL, Chan J. Tuberculosis: latency and reactivation. Infect Immun 2001; 69: 4195–201PubMedCrossRefGoogle Scholar
  15. 15.
    Orme I. The latent tuberculosis bacillus (I’ll let you know if I ever meet one). Int J Tuberc Lung Dis 2001; 5: 589–93PubMedGoogle Scholar
  16. 16.
    Iseman MD. A clinician’s guide to tuberculosis. Philadelphia: Lippencott Williams & Wilkins, 2000: 271–321Google Scholar
  17. 17.
    American Thoracic Society. Treatment of tuberculosis and tuberculosis infection in adults and children. Am J Respir Crit Care Med 1994; 149: 1359–74Google Scholar
  18. 18.
    Kreis B, Pretet S. Two three-month treatment regimens for pulmonary tuberculosis. Bull Int Union Tuberc 1976; 51: 71–5PubMedGoogle Scholar
  19. 19.
    Girling DJ. Adverse effects of antituberculous drugs. Drugs 1982; 23: 56–74PubMedCrossRefGoogle Scholar
  20. 20.
    Burman WJ, Gallicano K, Peloquin CA. Comparative pharmacokinetics and pharmacodynamics of the rifamycin antibiotics. Clin Pharmacokinet 2001; 40: 327–41PubMedCrossRefGoogle Scholar
  21. 21.
    Burman WJ, Dalton CB, Cohn DL, et al. A cost-effectiveness analysis of directly observed therapy vs. self-administered therapy for treatment of tuberculosis. Chest 1997; 112: 63–70PubMedCrossRefGoogle Scholar
  22. 22.
    British Thoracic Association. A controlled trial of six months chemotherapy in pulmonary tuberculosis. Br J Dis Chest 1981; 75: 141–53CrossRefGoogle Scholar
  23. 23.
    Vernon A, for the TB Trials Consortium. TBTC Study 22 (Rifapentine Trial): Preliminary Results in HIV-negative Patients [abstract]. Am J Respir Crit Care Med 2000; 161: A252Google Scholar
  24. 24.
    Kimerling ME, Phillips P, Patterson P, et al. Low serum antimycobacterial drug levels in non-HIV-infected tuberculosis patients. Chest 1998; 113: 1178–83PubMedCrossRefGoogle Scholar
  25. 25.
    Yew WW. Therapeutic drug monitoring in antituberculosis chemotherapy. Ther Drug Monit 1998; 20(5): 469–72PubMedCrossRefGoogle Scholar
  26. 26.
    Mehta JR, Shantaveerapa H, Byrd RP, et al. Utility of rifampin blood levels in the treatment and follow-up of active pulmonary tuberculosis patients who were slow to respond to routine directly observed therapy. Chest 2001; 120: 1520–4PubMedCrossRefGoogle Scholar
  27. 27.
    Weiner M, Khan A, Benator D, et al. Low isoniazid levels are associated with tuberculosis treatment failure or relapse with once-weekly rifapentine and isoniazid [abstract]. Proceedings of the 97th American Lung Association / American Thoracic Society International Conference; 2001 May 18–23; San Francisco (CA). Am J Respir Crit Care Med 2001; 163: A–498Google Scholar
  28. 28.
    Peloquin CA, Benator D, Hayden K, et al. Low rifapentine, rifampin, & isoniazid plasma levels are not predicted by clinical and demographic features [abstract]. Proceedings of the 97th American Lung Association / American Thoracic Society International Conference; 2001 May 18–23; San Francisco (CA). Am J Respir Crit Care Med 2001; 163: A–498Google Scholar
  29. 29.
    Peloquin CA. Tuberculosis Drug Serum Levels (letter). Clin Infect Dis 2001; 33: 584–5PubMedCrossRefGoogle Scholar
  30. 30.
    Peloquin CA. Pharmacological issues in the treatment of tuberculosis. Ann N Y Acad Sci 2001; 953: 157–64PubMedCrossRefGoogle Scholar
  31. 31.
    Jelliffe R. Goal-oriented, model-based drug regimens: setting individualized goals for each patient. Ther Drug Monit 2000; 22: 325–9PubMedCrossRefGoogle Scholar
  32. 32.
    Holdiness MR. Clinical pharmacokinetics of the antituberculosis drugs. Clin Pharmacokinet 1984; 9: 511–44PubMedCrossRefGoogle Scholar
  33. 33.
    Peloquin CA. Antituberculosis drugs: pharmacokinetics. In: Heifets L, editor. Drug susceptibility in the chemotherapy of mycobacterial infections. Boca Raton: CRC Press; 1991: 59–88Google Scholar
  34. 34.
    Steil CF. Diabetes mellitus. In: DiPiro JT, Talbert RL, Yee GC, et al., editors. Pharmacotherapy: a pathophysiologic approach. 4th ed. Stamford (CT): Appleton & Lange, 1999: 1219–43Google Scholar
  35. 35.
    Bashar M, Alcabes P, Rom WN, et al. Increased incidence of multidrug-resistant tuberculosis in diabetic patients on the Bellevue Chest Service, 1987–1997. Chest 2001; 120: 1514–9PubMedCrossRefGoogle Scholar
  36. 36.
    Kotier DP, Gaetz HP, Lange M, et al. Enteropathy associated with the acquired immunodeficiency syndrome. Ann Intern Med 1984; 101: 421–8Google Scholar
  37. 37.
    Gillin JS, Shike M, Alcock N, et al. Malabsorption and mucosal abnormalities of the small intestine in the acquired immunodeficiency syndrome. Ann Intern Med 1985; 102: 619–22PubMedGoogle Scholar
  38. 38.
    Bartlett JG, Belitsos PC, Sears CL. AIDS enteropathy. Clin Infect Dis 1992; 15: 726–35PubMedCrossRefGoogle Scholar
  39. 39.
    Berning SE, Huitt GA, Iseman MD, et al. Malabsorption of Anti-tuberculosis medications by a patient with AIDS [letter]. N Engl J Med 1992; 327: 1817–8PubMedCrossRefGoogle Scholar
  40. 40.
    Peloquin CA, MacPhee AA, Berning SE. Malabsorption of antimycobacterial medications. N Engl J Med 1993; 329: 1122–3PubMedCrossRefGoogle Scholar
  41. 41.
    Gordon SM, Horsburgh CR, Peloquin CA, et al. Low serum levels of oral antimycobacterial agents in patients with disseminated Mycobacterium avium complex disease. J Infect Dis 1993; 168: 1559–62PubMedCrossRefGoogle Scholar
  42. 42.
    Colborn D, Lewis R, Narang P. HIV disease does not influence rifabutin absorption [abstract no. A42]. Proceedings of the 34th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1994 Oct 4–7; Orlando (FL)Google Scholar
  43. 43.
    Patel KB, Belmonte R, Crowe HM. Drug malabsorption and resistant tuberculosis in HIV-infected patients [letter]. N Engl J Med 1995; 332: 336–7PubMedCrossRefGoogle Scholar
  44. 44.
    Peloquin CA, Nitta AT, Burman WJ, et al. Incidence of low anti-tuberculosis drug concentrations in patients with AIDS. Ann Pharmacother 1996; 30: 919–25PubMedGoogle Scholar
  45. 45.
    Choudhri SH, Hawken M, Gathua S, et al. Pharmacokinetics of antimycobacterial drugs in patients with tuberculosis, AIDS, and diarrhea. Clin Infect Dis 1997; 25: 104–11PubMedCrossRefGoogle Scholar
  46. 46.
    Sahai J, Gallicano K, Swick L, et al. Reduced plasma concentrations of antituberculous drugs in patients with HIV infection. Ann Intern Med. 1997; 127: 289–93PubMedGoogle Scholar
  47. 47.
    Peloquin CA. Serum Concentrations of the Antimycobacterial Drugs. Chest 1998; 113: 1154–5PubMedCrossRefGoogle Scholar
  48. 48.
    Taylor B, Smith PJ. Does AIDS impair the absorption of the antituberculosis agents? Int J Tuberc Lung Dis 1998; 2: 670–5PubMedGoogle Scholar
  49. 49.
    Peloquin CA, Berning SE, Huitt GA, et al. AIDS and TB drug absorption [letter]. Int J Tuberc Lung Dis 1999; 3: 1143–4PubMedGoogle Scholar
  50. 50.
    Jaruratanasirikul S. The pharmacokinetics of oral rifampicin in AIDS patients. J Med Assoc Thai 1998; 81: 25–8PubMedGoogle Scholar
  51. 51.
    Burman WJ, Gallicano K, Peloquin CA. Therapeutic implications of drug interactions in the treatment of HIV-related tuberculosis. Clin Infect Dis 1999; 28: 419–30PubMedCrossRefGoogle Scholar
  52. 52.
    Perlman DC, Remmel R, Brundage R, et al., for the ACTG 309 Protocol Team. Pharmacokinetics of antituberculous agents in persons with HIV-related tuberculosis [abstract no. 619]. Proceedings of the Infectious Diseases Society 37th Annual Meeting; 1999 Nov 18–21; Philadelphia (PA). Clin Infect Dis 1999; 29: 1070Google Scholar
  53. 53.
    Narita M, Hisada M, Thimmappa B, et al. Tuberculosis recurrence: multivariate analysis of serum levels of tuberculosis drugs, human immunodeficiency virus status, and other risk factors. Clin Infect Dis 2001; 32: 515–7PubMedCrossRefGoogle Scholar
  54. 54.
    Narita M, Stambaugh JJ, Hollender ES, et al. Use of rifabutin with protease inhibitors for HIV-infected tuberculosis patients. Clin Infect Dis 2000; 30: 779–83PubMedCrossRefGoogle Scholar
  55. 55.
    CDC. Prevention and treatment of tuberculosis among patients infected with human Immunodeficiency Virus: principles of therapy and revised recommendations. Morb Mortal Wkly Rep 1998; 47(RR-20): 1–58Google Scholar
  56. 56.
    CDC. Updated guidelines for the use of rifabutin or rifampin for the treatment and prevention of tuberculosis among HIV-infected patients taking protease inhibitors on nonnucleoside reverse transcriptase inhibitors. Morb Mortal Wkly Rep 2000; 49: 185–9Google Scholar
  57. 57.
    Finch CK, Chrisman CR, Baciewicz AM, et al. Rifampin and rifabutin drug interactions: an update. Arch Intern Med 2002; 162(9): 985–92PubMedCrossRefGoogle Scholar
  58. 58.
    Durant J, Clevenbergh P, Garraffo R, et al. Importance of protease inhibitor plasma levels in HIV-infected patients treated with genotypic-guided therapy: pharmacological data from the Viradapt Study. AIDS 2000; 14: 1333–9PubMedCrossRefGoogle Scholar
  59. 59.
    Piscitell SC. The value of drug levels: the plot thickens. Medscape.com 2001 [online]. Available from URL: http://id.medscape.com/medscape/cno/2001/RETRO/story.cfm?.story_id=2055 [Accessed 2002 Sep 3]
  60. 60.
    Acosta EP, Kakuda TN, Brundage RC, et al. Pharmacodynamics of Human Immunodeficiency Virus Type 1 Protease Inhibitors. Clin Infect Dis 2000; 30 Suppl. 2: S151–9PubMedCrossRefGoogle Scholar
  61. 61.
    Angel JB, Khaliq Y, Monpetit ML, et al. An argument for routine therapeutic drug monitoring of HIV-1 protease inhibitors during pregnancy. AIDS 2001; 15: 417–9PubMedCrossRefGoogle Scholar
  62. 62.
    Back D, Gatti G, Fletcher C, et al. Therapeutic drug monitoring in HIV infection: current status and future directions. AIDS 2002; 16 Suppl. 1: S5–S37PubMedCrossRefGoogle Scholar
  63. 63.
    Cuss FMC, Carmichael DJS, Linington A, et al. Tuberculosis in renal failure: a high incidence in patients born in the third world. Clin Nephrology 1986; 25: 129–33Google Scholar
  64. 64.
    Tokars JI, Miller ER, Alter MJ, et al. National surveillance of dialysis associated diseases in the United States, 1995. ASAIOJ 1998; 44: 98–107CrossRefGoogle Scholar
  65. 65.
    Cengiz K. Increased incidence of tuberculosis in patients undergoing hemodialysis. Nephron 1996; 73: 421–4PubMedCrossRefGoogle Scholar
  66. 66.
    Chia S, Karim M, Elwood RK, et al. Risk of tuberculosis in dialysis patients: a population-based study. Int J Tuberc Lung Dis 1998; 2(12): 989–91PubMedGoogle Scholar
  67. 67.
    Malone RS, Fish DN, Spiegel DM, et al. The effect of hemodialysis on isoniazid, rifampin, pyrazinamide, and ethambutol. Am J Respir Crit Care Med 1999; 159: 1580–4PubMedGoogle Scholar
  68. 68.
    Malone RS, Fish DN, Spiegel DM, et al. The effect of hemodialysis on cycloserine, ethionamide, para-aminosalicylate, and clofazimine. Chest 1999; 116: 984–90PubMedCrossRefGoogle Scholar
  69. 69.
    Peloquin CA, Jaresko GS, Yong CL, et al. Population Pharmacokinetic Modeling of Isoniazid, Rifampin, and Pyrazinamide. Antimicrobial Agents Chemother 1997; 41: 2670–9Google Scholar
  70. 70.
    Peloquin CA, Namdar R, Dodge AA, et al. Pharmacokinetics of Isoniazid Under Fasting Conditions, with Food, and with Antacids. Int J Tuberc Lung Dis 1999; 3: 703–10PubMedGoogle Scholar
  71. 71.
    Weiner M, Khan A, Benator D, et al., and the TB Trials Consortium. Low Isoniazid (INH) Levels Are Associated with TB Treatment Failure/Relapse with Once-Weekly Rifapentine (RPT) and INH [abstract]. Am J Respir Crit Care Med 2001; 163: A498Google Scholar
  72. 72.
    Acocella G. Pharmacokinetics and metabolism of rifampin in humans. Rev Infect Dis 1983; 5: S428–32PubMedCrossRefGoogle Scholar
  73. 73.
    Cavenaghi R. Rifampicin raw material characteristics and their effect on bioavailability. Bull Int Union Tuberc Lung Dis 1989; 64: 36–7PubMedGoogle Scholar
  74. 74.
    Peloquin CA, Namdar R, Singleton MD, et al. Pharmacokinetics of Rifampin Under Fasting Conditions, with Food, and with Antacids. Chest 1999; 115: 12–8PubMedCrossRefGoogle Scholar
  75. 75.
    McEvoy GK, editor. AHFS Drug Information. Bethesda (MD): American Soc Health-Systems Pharmacists, 2002: 482–527Google Scholar
  76. 76.
    Ellard GA, Fourie PB. Rifampicin bioavailability: a review of its pharmacology and the chemotherapeutic necessity for ensuring optimal absorption. Int J Tuberc Lung Dis 1999; 3: S301–8PubMedGoogle Scholar
  77. 77.
    Kucers A, Bennett N. The use of antibiotics. 4th ed. Philadelphia: J.B. Lippencott Company, 1987: 914–70Google Scholar
  78. 78.
    Nahata MC, Temple ME. Rifapentine: Its role in the treatment of tuberculosis. Ann Pharmacother 1999; 33: 1203–10PubMedCrossRefGoogle Scholar
  79. 79.
    Tarn CM, Chan SL, Kam KM, et al. Rifapentine and isoniazid in the continuation phase of a 6-month regimen. Interim report: no activity of isoniazid in the continuation phase. Int J Tuberc Lung Dis 2000; 4: 262–7Google Scholar
  80. 80.
    Mitchison DA. Development of rifapentine: the way ahead. Int J Tuberc Lung Dis 1998; 2: 612–5PubMedGoogle Scholar
  81. 81.
    Bock N, Sterling T, Pachucki C, et al. for the TB Trials Consortium. Tolerability of once-weekly rifapentine 900 mg plus INH vs once-weekly rifapentine 600 mg plus INH during continuation phase treatment of pan-susceptible tuberculosis in HIV-negative adults [abstract + poster]. Am J Respir Crit Care Med 2001; 163: A497Google Scholar
  82. 82.
    Nightingale CH. Moxifloxacin, a new antibiotic designed to treat community-acquired respiratory tract infections: A review of microbiologic and pharmacokinetic-pharmacodynamic characteristics. Pharmacotherapy 2000; 20: 245–56PubMedCrossRefGoogle Scholar
  83. 83.
    Perry CM, Barman Balfour JA, Lamb HM. Gatifloxacin. Drugs 1999; 58: 683–96PubMedCrossRefGoogle Scholar
  84. 84.
    Fish DN, Chow AT. The clinical pharmacokinetics of levofloxacin. Clin Pharmacokinet 1997; 32: 101–19PubMedCrossRefGoogle Scholar
  85. 85.
    Berning SE, Madsen L, Iseman MD, et al. Long-term safety of ofloxacin and ciprofloxacin in the treatment of Mycobacterial infections. Am J Respir Crit Care Med 1995; 151: 2006–9PubMedGoogle Scholar
  86. 86.
    Peloquin CA, Berning SE, Madsen L, et al. Ofloxacin and Ciprofloxacin in the Treatment of Mycobacterial Infections: Development of Resistance and Drug Interactions. J Infect Dis Pharmacother 1995; 1: 45–65CrossRefGoogle Scholar
  87. 87.
    Berning SE. The role of fluoroquinolones in tuberculosis today. Drugs 2001; 61: 9–18PubMedCrossRefGoogle Scholar
  88. 88.
    Peloquin CA, Bulpitt AE, Jaresko GS, et al. Pharmacokinetics of Pyrazinamide Under Fasting Conditions, with Food, and with Antacids. Pharmacotherapy 1998; 18: 1205–11PubMedGoogle Scholar
  89. 89.
    Weiner IM, Tinker JP. Pharmacology of pyrazinamide: Metabolic and renal function studies related to the mechanism of drug-induced urate retention. J Pharmacol Exp Ther 1972; 180: 411–34PubMedGoogle Scholar
  90. 90.
    Horn DL, Hewlett Jr D, Alfalla C, et al. Limited tolerance of ofloxacin and pyrazinamide prophylaxis against tuberculosis [letter]. N Engl J Med 1994; 330: 1241PubMedCrossRefGoogle Scholar
  91. 91.
    Peloquin CA, Bulpitt AE, Jaresko GS, et al. Pharmacokinetics of ethambutol under fasting conditions, with food, and with antacids. Antimicrobial Agents Chemother 1999, 43; 568–72Google Scholar
  92. 92.
    Peloquin CA. Mycobacterium avium complex infection: pharmacokinetic and pharmacodynamic considerations that may improve clinical outcomes. Clin Pharmacokinet 1997; 32: 132–44PubMedCrossRefGoogle Scholar
  93. 93.
    Zhu M, Burman WJ, Jaresko GS, et al. Population pharmacokinetics of intravenous and intramuscular streptomycin in patients with tuberculosis. Pharmacotherapy 2001; 21: 1037–45PubMedCrossRefGoogle Scholar
  94. 94.
    Demczar DJ, Nafziger AN, Bertino JS Jr. Pharmacokinetics of gentamicin at traditional versus high doses: implications for once-daily aminoglycoside dosing. Antimicrobial Agents Chemother 1997; 41: 1115–9Google Scholar
  95. 95.
    Peloquin CA, Henshaw TL, Huitt GA, et al. Pharmacokinetic evaluation of p-aminosalicylic acid granules [published erratum appears in Pharmacotherapy 1994; 14: (4) P-2]. Pharmacotherapy 1994; 14: 40–6PubMedGoogle Scholar
  96. 96.
    Peloquin CA, Berning SE, Huitt GA, et al. Once-daily and twice-daily dosing of p-aminosalicylic acid (PAS) granules. Am J Respir Crit Care Med 1999; 159: 932–4PubMedGoogle Scholar
  97. 97.
    Peloquin CA, Zhu M, Adam RD, et al. Pharmacokinetics of p-aminosalicylate underfasting conditions, with orange juice, food, and antacids. Ann Pharmacother 2001; 35: 1332–8PubMedCrossRefGoogle Scholar
  98. 98.
    Berning SE, Peloquin CA. Antimycobacterial agents: Cycloserine. In: Yu VL, Merigan TC, Barriere S, White NJ, editors. Antimicrobial chemotherapy and vaccines. Baltimore (MD): Williams and Wilkins, 1998: 638–42Google Scholar
  99. 99.
    Zhu M, Nix DE, Adam RD, et al. Pharmacokinetics of cycloserine underfasting conditions, with orange juice, food, and antacids. Pharmacotherapy 2001; 21: 891–7PubMedCrossRefGoogle Scholar
  100. 100.
    Berning SE, Peloquin CA. Antimycobacterial agents: Ethionamide. In: Yu VL, Merigan TC, Barriere S, White NJ, editors. Antimicrobial chemotherapy and vaccines. Baltimore (MD): Williams and Wilkins, 1998: 650–4Google Scholar
  101. 101.
    Auclair B, Nix DE, Adam RD, et al. Pharmacokinetics of ethionamide under fasting conditions, with orange juice, food, and antacids. Antimicrobial Agents Chemother 2001; 45: 810–4CrossRefGoogle Scholar
  102. 102.
    Garrelts JC. Clofazimine: a review of its use in leprosy and Mycobacterium avium complex infection. DICP Ann Pharmacother 1991; 25: 525–31Google Scholar

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© Adis International Limited 2002

Authors and Affiliations

  1. 1.Department of MedicineNational Jewish Medical and Research CenterDenverUSA
  2. 2.Schools of Pharmacy and MedicineUniversity of ColoradoDenverUSA

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