title: Intracellular and plasma pharmacokinetics of 400 mg of etravirine once daily versus 200 mg of etravirine twice daily in HIV-infected patients.
abstract: OBJECTIVE
  To compare intracellular and plasma etravirine concentrations when etravirine was given at 200 mg/12 h versus 400 mg/24 h and to evaluate whether the results would support once-daily dosing.
  
  
  METHODS
  This was an open-label sequential study in which eight patients on protease inhibitor (PI)-sparing regimens containing etravirine were included. Full pharmacokinetic profiles were performed while on 200 mg of etravirine/12 h and after switching to 400 mg of etravirine/24 h. Intracellular and plasma levels were determined by liquid chromatography coupled with mass spectrometry. Pharmacokinetic parameters were calculated by non-compartmental analysis and compared by geometric mean ratios (GMRs) using 200 mg of etravirine/12 h as the reference group.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01121809.
  
  
  RESULTS
  The geometric mean (GM) for etravirine AUC(0-τ) (5602 versus 5076 ng · h/mL, GMR 0.91), C(max) (403 versus 495 ng/mL, GMR 1.23) and C(min) (139 versus 102 ng/mL, GMR 0.74) were similar with both dosing schedules at the intracellular level. In plasma, the GMRs for AUC(0-τ), C(max) and C(min) were 1.31, 1.76 and 0.99, respectively. The mean intracellular penetration, evaluated as intracellular and plasma AUC(0-τ) ratios, was 81% when etravirine was dosed twice daily and 56% with once-daily dosing.
  
  
  CONCLUSIONS
  Our results show that intracellular etravirine levels were similar with both dosing regimens in patients with PI-sparing regimens, while etravirine plasma AUC(0-τ) and C(max) were 30% and 76% higher with the once-daily regimen, respectively. Thus, a once-daily dosing regimen is supported not only by plasma etravirine pharmacokinetic profiles but also by intracellular levels.
authors.affiliation: Unidad Clínica de Enfermedades Infecciosas, Hospitales Universitarios Virgen del Rocío/Instituto de Biomedicina de Sevilla, Seville, Spain. alicia.gutierrez.valencia@gmail.com
authors.forename: Alicia
authors.initials: A
authors.lastname: Gutiérrez-Valencia
authors.forename: Reyes
authors.initials: R
authors.lastname: Martin-Peña
authors.forename: Almudena
authors.initials: A
authors.lastname: Torres-Cornejo
authors.forename: Rosa
authors.initials: R
authors.lastname: Ruiz-Valderas
authors.forename: Juan R
authors.initials: JR
authors.lastname: Castillo-Ferrando
authors.forename: Luis F
authors.initials: LF
authors.lastname: López-Cortés
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001773:Blood Cells / Q000737:chemistry*; D002853:Chromatography, Liquid; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009570:Nitriles; D010949:Plasma / Q000737:chemistry*; D011724:Pyridazines / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011743:Pyrimidines
chemical_list: D019380:Anti-HIV Agents; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; C451734:etravirine