title: Pharmacokinetics of Raltegravir in HIV-Infected Patients on Rifampicin-Based Antitubercular Therapy.
abstract: BACKGROUND
  Rifampicin (RIF) induces UGT1A1, an enzyme involved in raltegravir (RAL) elimination, thereby potentially lowering RAL exposure. We examined the pharmacokinetics of RAL in human immunodeficiency virus (HIV)-infected patients on RIF-based antitubercular therapy in the French National Agency for HIV/AIDS and Viral Hepatitis Research 12 180 Reflate Tuberculosis trial.
  
  
  METHODS
  Patients started RAL in combination with tenofovir disoproxil fumarate and lamivudine after initiation of RIF (10 mg/kg/day). In arm 1 (n = 21), they received 400 mg RAL twice daily; in arm 2 (n = 16), they received RAL 800 mg twice daily initially then 400 mg twice daily 4 weeks after RIF discontinuation. Pharmacokinetic sampling was performed over 12-hour periods, 4 weeks after initiation of RAL together with RIF (period 1), 4 weeks after RIF discontinuation (period 2), and after the RAL dose reduction in arm 2 (period 3).
  
  
  RESULTS
  In arm 1, the geometric mean ratio (GMR) between period 1 and period 2 was 0.94 (90% confidence interval [CI], .64-1.37) for the 12-hour area under the time-concentration curve (AUC0-12), and 0.69 (90% CI, .42-1.13) for the concentration at 12 hours (C12). In arm 2, the corresponding GMRs were 0.75 (90% CI, .48-1.17) and 1.10 (90% CI, .61-2.00) for period 1 vs period 2, and 1.10 (90% CI, .78-1.55) and 1.68 (90% CI, .88-3.23) for period 1 vs period 3.
  
  
  CONCLUSIONS
  The double dose of RAL overcompensated for RIF induction, but the standard dose was associated with only small decreases in AUC0-12 and C12 during RIF coadministration, warranting further evaluation in patients with HIV/tuberculosis coinfection.
  
  
  BACKGROUND
  NCT0082231.
authors.affiliation: Hospital Bicetre, Assistance Publique-Hôpitaux de Paris, DHU Hepatinov; INSERM U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Université Paris-Sud, Kremlin Bicêtre.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Taburet
authors.affiliation: Hospital Saint-Louis, Assistance Publique-Hôpitaux de Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Sauvageon
authors.affiliation: Instituto de Pesquisa Clinica Evandro Chagas, Fundaçao Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Grinsztejn
authors.affiliation: Centre INSERM U897-Epidémiologie-Biostatistiques, Université de Bordeaux, Bordeaux, France.
authors.forename: Alex
authors.initials: A
authors.lastname: Assuied
authors.affiliation: Instituto de Pesquisa Clinica Evandro Chagas, Fundaçao Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Valdilea
authors.initials: V
authors.lastname: Veloso
authors.affiliation: Hospital General de Nova Iguaçu and Laboratório de AIDS e Imunologia Molecular, Rio de Janeiro, Brazil.
authors.forename: José Henrique
authors.initials: JH
authors.lastname: Pilotto
authors.affiliation: Hospital Saint-Louis, Assistance Publique-Hôpitaux de Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: De Castro
authors.affiliation: Centre INSERM U897-Epidémiologie-Biostatistiques, Université de Bordeaux, Bordeaux, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Grondin
authors.affiliation: Centre INSERM U897-Epidémiologie-Biostatistiques, Université de Bordeaux, Bordeaux, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Fagard
authors.affiliation: Hospital Saint-Louis, Assistance Publique-Hôpitaux de Paris, France University Paris Diderot INSERM U941, Paris, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000904:Antibiotics, Antitubercular / Q000627:therapeutic use*; D060085:Coinfection; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D000068898:Raltegravir Potassium / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012293:Rifampin / Q000627:therapeutic use*; D000068698:Tenofovir / Q000008:administration & dosage / Q000627:therapeutic use; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D019380:Anti-HIV Agents; D000904:Antibiotics, Antitubercular; D019259:Lamivudine; D000068898:Raltegravir Potassium; D000068698:Tenofovir; D012293:Rifampin
keywords: HIV; pharmacokinetics; raltegravir; rifampicin; tuberculosis