Clinical Pharmacokinetics

, Volume 41, Issue 9, pp 681–690 | Cite as

Pharmacokinetic Interactions Between Efavirenz and Rifampicin in HIV-Infected Patients with Tuberculosis

  • Luis F. López-Cortés
  • Rosa Ruiz-Valderas
  • Pompeyo Viciana
  • Aristides Alarcón-González
  • Jesús Gómez-Mateos
  • Eva León-Jimenez
  • Maria Sarasa-Nacenta
  • Yolanda López-Pua
  • Jerónimo Pachón
Original Research Article



To evaluate the pharmacokinetic interactions between efavirenz and rifampicin (rifampin) in patients with HIV infection and tuberculosis.


Nonblind, randomised, pharmacokinetic study.


24 patients (21 male, 3 female; mean age 37 years) with HIV infection and tuberculosis.


Patients were randomised to one of the following treatments: group A (n = 16) received antituberculosis drugs without rifampicin, plus highly active antiretroviral therapy (HAART) including efavirenz 600mg once daily, on days 1 to 7. Patients were then switched to rifampicin in bodyweight-adjusted fixed-dose combination plus HAART including efavirenz 600mg once daily (group A-1; n = 8) or efavirenz 800mg once daily (group A-2; n = 8). Group B (n = 8) received rifampicin in bodyweight-adjusted fixed-dose combination on days 1 to 7; on day 8, HAART including efavirenz 800mg once daily was added. Blood samples were obtained on days 7 and 14.


Plasma concentrations of efavirenz and rifampicin were quantified by using validated high performance liquid chromatography assays, and pharmacokinetic parameter values were determined by noncompartmental methods. The differences between pharmacokinetic parameters on days 7 and 14 were used to assess interactions.


There was a correlation between the pharmacokinetic parameters of efavirenz and the dose/kg administered. For efavirenz, mean (median) peak concentration, trough concentration and area under the concentration-time curve over the administration interval decreased 24% (24%), 25% (18%) and 22% (10%), respectively, in the presence of rifampicin. Large interpatient variability was observed, suggesting that plasma concentration monitoring of efavirenz may be advisable. Overall, the pharmacokinetics of efavirenz 800mg plus rifampicin were similar to those of efavirenz 600mg without rifampicin. The pharmacokinetics of rifampicin did not change substantially in the presence of efavirenz. Differences in patients’ bodyweight appeared to cause further differences in exposure to efavirenz. Plasma concentrations of efavirenz in patients weighing <50kg were similar to those previously described in HIV-infected patients without concomitant tuberculosis. However, plasma concentrations in patients weighing >50kg were almost halved compared with those in patients weighing <50kg.


Although the minimal effective efavirenz plasma concentration that assures virological success is not currently known, it may be advisable to increase the dosage of efavirenz to 800mg once daily when it is coadministered with rifampicin. Rifampicin can be used with efavirenz without dosage modification.


Rifampicin Efavirenz Rifabutin Rifamycin Antituberculosis Drug 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported with research funds from DuPont Pharma. The authors thank patients for their collaboration in the study, nurses for caring for these patients, Dr. A. Marin for her technical support, and DuPont Pharma for financial support.


  1. 1.
    Palella F, Delaney K, Moorman A, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med 1998; 338: 853–60PubMedCrossRefGoogle Scholar
  2. 2.
    Control de la tuberculosis en relación con la epidemia de infección por VIH/SIDA. Recomendaciones del Consejo Asesor Clínico del Plan Nacional sobre el SIDA; 1999 Jul; Spain: Número 14Google Scholar
  3. 3.
    Poznial AL, Miller R, Ormerod LP. The treatment of tuberculosis in HIV-infected persons. AIDS 1999; 13: 435–45CrossRefGoogle Scholar
  4. 4.
    Centers for Disease Control and Prevention. Prevention and treatment of tuberculosis among patients infected with human immunodeficiency virus: principles of therapy and revised recommendations. MMWR 1998; 47: 1–58Google Scholar
  5. 5.
    Centers for Disease Control and Prevention. Clinical update: impact of HIV protease inhibitors on the treatment of HIV infected tuberculosis patients with rifampin. MMWR 1996; 45: 921–9258Google Scholar
  6. 6.
    US Department of Health and Human Services. Updated guidelines for the use of rifabutin or rifampin for the treatment and prevention of tuberculosis among HIV-infected patients taking protease inhibitors or nonnucleoside reverse transcriptase inhibitors. MMWR 2000; 49: 185–99Google Scholar
  7. 7.
    Veldkamp AI, Hoetelmans MW, Beijnen JH, et al. Ritonavir enables combined therapy with rifampin and saquinavir [letter]. Clin Infect Dis 1999; 29: 1586PubMedCrossRefGoogle Scholar
  8. 8.
    Squires K, Hammer S, Degruttola V, et al. Randomized trial of abacavir (ABC) in combination with indinavir (IDV) and efavirenz (EFV) in HIV-infected patients (Pts) with nucleoside analog experience (NRTI exp) [abstract]. Proceeding of the 6th Conference on Retroviruses and Opportunistic Infections; 1999 Jan 31; Chicago: LB15Google Scholar
  9. 9.
    Staszewski S, Morales-Ramirez J, Tashima KT, et al. Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. N Engl J Med 1999; 341: 1865–73PubMedCrossRefGoogle Scholar
  10. 10.
    Benedek IH, Joshi A, Fiske SJ, et al. Pharmacokinetic interaction between efavirenz (EFV) and rifampin (RIF) in healthy volunteers [abstract]. Proceeding of the 12th World AIDS Conference; 1998 June 28; Geneva: 42280Google Scholar
  11. 11.
    Sarasa-Nacenta M, López-Púa Y, López-Cortés LF, et al. Determination of efavirenz in human plasma by high-performance liquid chromatography with ultraviolet detection. J Chromatogr B 2001; 763: 53–9CrossRefGoogle Scholar
  12. 12.
    Jamaluddin ABM, Sarwar G, Rahim MA, et al. Highperformance liquid Chromatographic assay of rifampicin in human serum. J Chromatogr 1990; 525: 495–7PubMedCrossRefGoogle Scholar
  13. 13.
    European Agency for the Evaluation of Medicinal Products. Efavirenz (Sustiva®): summary of product characteristics [online]. Available from: [Accessed 2002 Jun 29]
  14. 14.
    BMS Virology. Efavirenz (Sustiva®): prescribing information. Princeton (NJ): Bristol-Myers Squibb, April 2002Google Scholar
  15. 15.
    US Department of Health and Human Services. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents [online]. Updated February 4 2002. Available from [Accessed 2002 Jun 29]
  16. 16.
    Villani P, Regazzi MB, Castelli F, et al. Pharmacokinetics of efavirenz alone and in combination therapy with nelfinavir in HIV-infected patients. Br J Clin Pharmacol 1999; 48: 712–5PubMedCrossRefGoogle Scholar
  17. 17.
    Kenny MT, States B. Metabolism and pharmacokinetics of the antibiotic rifampin. Drug Metab Rev 1981; 12: 159–218PubMedCrossRefGoogle Scholar
  18. 18.
    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
  19. 19.
    Polasa K, Murthy KJ, Krishnaswamy K. Rifampin kinetics in undernutrition. Br J Clin Pharmacol 1984; 17: 481–4PubMedCrossRefGoogle Scholar
  20. 20.
    Gordon SM, Horsburgh Jr 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
  21. 21.
    Peloquin CA, Nitta AT, Burman WJ, et al. Low antituberculosis drug concentrations in patients with AIDS. Ann Pharmacother 1996; 30: 919–25PubMedGoogle Scholar
  22. 22.
    Sahai J, Gallicano K, Swick L, et al. Reduced plasma concentrations of antituberculosis drugs in patients with HIV infection. Ann Intern Med 1997; 127: 289–93PubMedGoogle Scholar
  23. 23.
    Joshi AS, Barret JS, Fiske WD, et al. Population pharmacokinetics of efavirenz in phase II studies and relationship with efficacy [abstract]. Proceeding of the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1999 Sep 26-29; San Francisco: 1201Google Scholar
  24. 24.
    Marzolini C, Telenti A, Decosterd LA, et al. Efavirenz plasma levels can predict treatment failure and cental nervous system side effects in HIV-1-infected patients. AIDS 2001; 15: 71–5PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2002

Authors and Affiliations

  • Luis F. López-Cortés
    • 1
  • Rosa Ruiz-Valderas
    • 1
  • Pompeyo Viciana
    • 1
  • Aristides Alarcón-González
    • 1
  • Jesús Gómez-Mateos
    • 2
  • Eva León-Jimenez
    • 1
  • Maria Sarasa-Nacenta
    • 3
  • Yolanda López-Pua
    • 3
  • Jerónimo Pachón
    • 1
  1. 1.Infectious Diseases ServiceUniversity Hospital Virgen del RocíoSevilleSpain
  2. 2.Infectious Diseases UnitUniversity Hospital ValmeSevilleSpain
  3. 3.Pharmacology DepartmentHospital ClinicBarcelonaSpain

Personalised recommendations