title: Pharmacokinetics of an indinavir-ritonavir-fosamprenavir regimen in patients with human immunodeficiency virus.
abstract: OBJECTIVE
  To evaluate the pharmacokinetic compatibility of a ritonavir-boosted indinavir-fosamprenavir combination among patients with human immunodeficiency virus (HIV).
  
  
  METHODS
  Single-center, nonrandomized, prospective, multiple-dose, two-phase pharmacokinetic study.
  
  
  METHODS
  University research center.
  
  
  METHODS
  Eight adult patients with HIV infection who had been receiving and tolerating indinavir 800 mg-ritonavir 100 mg twice/day for at least 2 weeks. Intervention. After 12-hour pharmacokinetic sampling was performed on all patients (period A), fosamprenavir (a prodrug of amprenavir) 700 mg twice/day was coadministered for 5 days, with a repeat 12-hour pharmacokinetic sampling performed on the fifth day (period B).
  
  
  RESULTS
  Pharmacokinetic parameters were determined for indinavir, ritonavir, and amprenavir: area under the concentration-time curve from time 0 to 12 hours after dosing (AUC(0-12)), maximum plasma concentration (C(max)), and 12-hour plasma concentration (C(12)). For each parameter, the geometric mean, as well as the geometric mean ratio (GMR) comparing period B with period A, were calculated. Indinavir C(max) was lowered by 20% (GMR 0.80, 95% confidence interval [CI] 0.67-0.96), AUC(0-12) was lowered by 6% (GMR 0.94, 95% CI 0.74-1.21), and C(12) was increased by 28% (GMR 1.28, 95% CI 0.78-2.10). Ritonavir AUC(0-12) was 20% lower (GMR 0.80, 95% CI 0.54-1.19), C(max) was 15% lower (GMR 0.85, 95% CI 0.55-1.32), and C(12) was 7% lower (GMR 0.93, 95% CI 0.49-1.76). With the exception of indinavir C(max), the changes in indinavir and ritonavir pharmacokinetic parameters observed after fosamprenavir coadministration were not statistically significant. The geometric means of amprenavir AUC(0-12), C(max), and C(12) were 41,517 ng*hour/ml (95% CI 30,317-56,854 ng*hr/ml), 5572 ng/ml (95% CI 4330-7170 ng/ml), and 2421 ng/ml (95% CI 1578-3712 ng/ml), respectively.
  
  
  CONCLUSIONS
  The combination of indinavir 800 mg-ritonavir 100 mg-fosamprenavir 700 mg twice/day appears to be devoid of a clinically significant drug-drug interaction and should be evaluated as an alternative regimen in salvage HIV treatment. This combination may be suitable as part of a background regimen to optimize the therapeutic benefit of newer classes of antiretroviral agents such as the integrase and coreceptor inhibitors in the treatment of multidrug-resistant viruses.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, School of Medicine, Emory University, Atlanta, Georgia 30303, USA. iofotok@emory.edu
authors.forename: Ighovwerha
authors.initials: I
authors.lastname: Ofotokun
authors.forename: Edward P
authors.initials: EP
authors.lastname: Acosta
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Lennox
authors.forename: Yi
authors.initials: Y
authors.lastname: Pan
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Easley
mesh_terms: D000328:Adult; D019540:Area Under Curve; D002219:Carbamates / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005663:Furans; D006678:HIV / Q000187:drug effects* / Q000254:growth & development; D015658:HIV Infections / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D019469:Indinavir / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010755:Organophosphates / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011355:Prodrugs / Q000493:pharmacokinetics / Q000627:therapeutic use; D019438:Ritonavir / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013449:Sulfonamides / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D010755:Organophosphates; D011355:Prodrugs; D013449:Sulfonamides; D019469:Indinavir; D019438:Ritonavir; C426859:fosamprenavir