title: Steady-state pharmacokinetics of etravirine and lopinavir/ritonavir melt extrusion formulation, alone and in combination, in healthy HIV-negative volunteers.
abstract: BACKGROUND
  A previous study investigating coadministration of etravirine, a nonnucleoside reverse transcriptase inhibitor, and lopinavir/ritonavir soft-gel formulation resulted in nonclinically relevant changes in etravirine and lopinavir exposure. The current study evaluated the pharmacokinetic interaction between etravirine and the lopinavir/ritonavir melt extrusion formulation.
  
  
  METHODS
  Sixteen human immunodeficiency virus (HIV)-negative volunteers were randomized to either treatment sequence A/B or B/A, with 14 days- washout between treatments (treatment A: etravirine 200 mg bid for 8 days; treatment B: lopinavir/ritonavir 400/100 mg bid for 16 days with etravirine 200 mg bid on days 9-16). Steady-state pharmacokinetics were assessed for all antiretrovirals alone and coadministered; pharmacokinetic parameters were obtained by noncompartmental analysis. Safety and tolerability were assessed.
  
  
  RESULTS
  Coadministration of etravirine and lopinavir/ritonavir resulted in a 35% decrease in etravirine exposure. Smaller decreases (<13%) were observed in lopinavir and ritonavir exposure. Six volunteers reported headache; 1 grade 3 triglyceride increase was reported.
  
  
  CONCLUSIONS
  Lopinavir/ritonavir induced etravirine metabolism to a similar extent as most other boosted HIV protease inhibitors. The short-term coadministration of etravirine and lopinavir/ritonavir was well tolerated and did not lead to increased incidences of adverse events.
authors: Tibotec BVBA, Beerse, Belgium.
authors: Monika
authors: M
authors: Schöller-Gyüre
authors: Thomas N
authors: TN
authors: Kakuda
authors: James
authors: J
authors: Witek
authors: Sophie H
authors: SH
authors: Akuma
authors: Goedele
authors: G
authors: De Smedt
authors: Kurt
authors: K
authors: Spittaels
authors: Veerle
authors: V
authors: Vyncke
authors: Richard M W
authors: RM
authors: Hoetelmans
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D005782:Gels; D015658:HIV Infections; D006801:Humans; D061466:Lopinavir / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D011724:Pyridazines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D011743:Pyrimidines; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D005782:Gels; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; C451734:etravirine; D061466:Lopinavir; D019438:Ritonavir