title: Pharmacokinetics and safety of GW433908 and ritonavir, with and without efavirenz, in healthy volunteers.
abstract: OBJECTIVE
  To evaluate the safety and pharmacokinetic interaction between GW433908, ritonavir (RTV), and efavirenz (EFV).
  
  
  METHODS
  In period 1, subjects received either a once daily (QD) regimen of GW433908 1395 mg + RTV 200 mg (Study 1) or a twice daily (bid) regimen of GW433908 700 mg + RTV 100 mg (Study 2) for 14 days. In period 2, subjects received EFV 600 mg QD with either the same GW433908 + RTV regimen as in period 1 (arm 1) or with a GW433908 + RTV regimen that included an additional 100 mg of RTV (arm 2) for 14 days. Amprenavir (APV) pharmacokinetic sampling and safety assessments were performed on the last day of each period.
  
  
  RESULTS
  Plasma APV exposure was not significantly altered when EFV was coadministered with GW433908 700 mg twice daily (BID) + RTV 100 mg BID. Plasma APV exposure was decreased when EFV was coadministered with GW433908 1395 mg QD + RTV 200 mg QD. However, administration of EFV with GW433908 1395 mg QD + RTV 300 mg QD (i.e., adding an extra 100 mg of RTV) was able to negate this interaction. Adverse events were consistent with prior data for each of the separate agents.
  
  
  CONCLUSIONS
  When EFV is coadministered with the GW433908 700 mg + RTV 100 mg BID regimen, no dosage adjustment is recommended. However, when EFV is coadministered with the GW433908 1400 mg + RTV 200 mg QD regimen, an increase to RTV 300 mg QD is needed to maintain plasma APV exposure.
authors.affiliation: GlaxoSmithKline, Five Moore Drive, 17.2231.2B, Research Triangle Park, NC 27709, USA.
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Wire
authors.forename: Charles
authors.initials: C
authors.lastname: Ballow
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Preston
authors.forename: Craig W
authors.initials: CW
authors.lastname: Hendrix
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Piliero
authors.forename: Yu
authors.initials: Y
authors.lastname: Lou
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Stein
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000097:blood; D019540:Area Under Curve; D048588:Benzoxazines; D002219:Carbamates; D002784:Cholesterol / Q000097:blood; D003521:Cyclopropanes; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D005663:Furans; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010755:Organophosphates / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D010078:Oxazines / Q000009:adverse effects / Q000493:pharmacokinetics*; D011355:Prodrugs / Q000009:adverse effects / Q000032:analysis / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000493:pharmacokinetics*; D013449:Sulfonamides / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D014280:Triglycerides / Q000097:blood
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D002219:Carbamates; D003521:Cyclopropanes; D005663:Furans; D010755:Organophosphates; D010078:Oxazines; D011355:Prodrugs; D013449:Sulfonamides; D014280:Triglycerides; C095108:amprenavir; D002784:Cholesterol; C098320:efavirenz; D019438:Ritonavir; C426859:fosamprenavir