title: Pharmacokinetic interaction of rifapentine and raltegravir in healthy volunteers.
abstract: OBJECTIVE
  Latent tuberculosis infection and tuberculosis disease are prevalent worldwide. However, antimycobacterial rifamycins have drug interactions with many antiretroviral drugs. We evaluated the effect of rifapentine on the pharmacokinetic properties of raltegravir.
  
  
  METHODS
  In this open-label, fixed-sequence, three-period study, 21 healthy volunteers were given: raltegravir alone (400 mg every 12 h for 4 days) on days 1-4 of Period 1; rifapentine (900 mg once weekly for 3 weeks) on days 1, 8 and 15 of Period 2 and raltegravir (400 mg every 12 h for 4 days) on days 12-15 of Period 2; and rifapentine (600 mg once daily for 10 scheduled doses) on days 1, 4-8 and 11-14 of Period 3 and raltegravir (400 mg every 12 h for 4 days) on days 11-14 of Period 3. Plasma raltegravir concentrations were measured. ClinicalTrials.gov database: NCT00809718.
  
  
  RESULTS
  In 16 subjects who completed the study, coadministration of raltegravir with rifapentine (900 mg once weekly; Period 2) compared with raltegravir alone resulted in the geometric mean of the raltegravir AUC from 0 to 12 h (AUC0-12) being increased by 71%; the peak concentration increased by 89% and the trough concentration decreased by 12%. Coadministration of raltegravir with rifapentine in Period 3 did not change the geometric mean of the raltegravir AUC0-12 or the peak concentration, but it decreased the trough concentration by 41%. Raltegravir coadministered with rifapentine was generally well tolerated.
  
  
  CONCLUSIONS
  The increased raltegravir exposure observed with once-weekly rifapentine was safe and tolerable. Once-weekly rifapentine can be used with raltegravir to treat latent tuberculosis infection in patients who are infected with HIV.
authors.affiliation: Medical Service, Department of Veterans Affairs Medical Center, San Antonio, TX, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Weiner
authors.forename: Eric F
authors.initials: EF
authors.lastname: Egelund
authors.forename: Melissa
authors.initials: M
authors.lastname: Engle
authors.forename: Melissa
authors.initials: M
authors.lastname: Kiser
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Prihoda
authors.forename: Jonathan A L
authors.initials: JA
authors.lastname: Gelfond
authors.forename: William
authors.initials: W
authors.lastname: Mac Kenzie
authors.forename: Charles A
authors.initials: CA
authors.lastname: Peloquin
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D010949:Plasma / Q000737:chemistry; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000068898:Raltegravir Potassium; D012293:Rifampin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D012293:Rifampin; C018421:rifapentine
keywords: HIV; antiretroviral therapy; integrase strand transfer inhibitor; latent tuberculosis infection; rifamycin