Pharmacokinetic interaction between rifampicin and the once-daily combination of saquinavir and low-dose ritonavir in HIV-infected patients with tuberculosis

Esteban Ribera*, Carlos Azuaje, Rosa M. Lopez, Pere Domingo, Adria Curran, Maria Feijoo, Leonor Pou, Paquita Sanchez, Maria Antonia Sambeat, Joan Colomer, Josep Lluis Lopez-Colomes, Manuel Crespo, Vicenc Falco, Imma Ocana, Albert Pahissa

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

38 Citations (Scopus)

Abstract

Objectives: To assess plasma steady-state pharmacokinetics (PK) of rifampicin, isoniazid, saquinavir and ritonavir in HIV and tuberculosis (TB) co-infected patients, and investigate potential interactions between TB drugs and protease inhibitors (Pis). Methods: Open-label, single-arm, sequential PK study including 22 patients with Hill infection and TB. During the first 2 months, patients received rifampicin, isoniazid and pyrazinamide, with or without ethambutol (first PK study, n = 22). Then patients stopped pyrazinamide and ethambutol and started once-daily antiretroviral therapy (ART) with didanosine, lamivudine, ritonavir (200 mg) and saquinavir (1600 mg) (second PK study, n = 18). Patients stopped all TB drugs after 9 months continuing the same ART (third PK study, n = 15). Differences between TB drug parameters in the first and second PK studies, and between Pi parameters in the second and third PK studies were used to assess interactions. Results: Rifampicin and isoniazid pharmacokinetics did not change substantially with saquinavir and ritonavir. A significant 39.5%, 34.9% and 48.7% reduction in median saquinavir AUC(0-24), C-max, and C-trough, respectively, was seen with rifampicin and isoniazid. Ritonavir AUC(0-24), C-max and C-trough decreased 42.5%, 49.6% and 64.3%, respectively, with rifampicin and isoniazid. Conclusions: There was a significant interaction between saquinavir, ritonavir and rifampicin, with reduction in median plasma concentrations of saquinavir and ritonavir. Saquinavir should be given with caution in patients receiving rifampicin. Twice-daily dosing or higher saquinavir doses in once-daily administration should be tested to obtain more appropriate plasma levels.

Original languageEnglish
Article number59
Pages (from-to)690-697
Number of pages8
JournalJournal of Antimicrobial Chemotherapy
Volume59
Issue number4
DOIs
Publication statusPublished - Apr 2007

Keywords

  • protease inhibitors
  • antiretroviral therapy
  • HIV infection
  • tuberculosis therapy
  • HUMAN-IMMUNODEFICIENCY-VIRUS
  • ACTIVE ANTIRETROVIRAL THERAPY
  • STEADY-STATE PHARMACOKINETICS
  • HEALTHY-VOLUNTEERS
  • HIV-1-INFECTED PATIENTS
  • PULMONARY TUBERCULOSIS
  • DAILY REGIMEN
  • MG
  • EFAVIRENZ
  • CAPSULES

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