title: The steady-state pharmacokinetics of nelfinavir in combination with tenofovir in HIV-infected patients.
abstract: BACKGROUND
  The nucleotide analogue, tenofovir, has been shown to lower plasma atazanavir levels in pharmacokinetic trials, an interaction that may be partly reversed by the addition of ritonavir, whereas plasma tenofovir levels are themselves raised when the drug is combined with lopinavir/ritonavir.
  
  
  OBJECTIVE
  To investigate the effect of tenofovir coadministration on the steady-state pharmacokinetics of nelfinavir in HIV-infected patients.
  
  
  METHODS
  Eighteen patients received nelfinavir 1250 mg twice daily plus prescribed nucleoside reverse transcriptase inhibitors for at least 14 days, with pharmacokinetic measurements performed on day 15. Treatment with nelfinavir was continued for another 7 days with the addition of 300 mg tenofovir once daily. Pharmacokinetic measurements were repeated on day 22. Plasma samples were analysed by liquid chromatography-tandem mass spectrometry for nelfinavir, its primary metabolite, M8, and tenofovir. The parameters AUC0-12, C0, Cmax and Tmax were compared for nelfinavir with and without tenofovir by calculating geometric mean ratios (GMRs) of the pharmacokinetic parameters with associated 95% confidence intervals (95% CIs). Safety was assessed throughout the study.
  
  
  RESULTS
  The addition of tenofovir to the nelfinavir-based regimen had no effect on the pharmacokinetics of nelfinavir. The GMR of the nelfinavir AUC0-12 values was 0.97 (95% CI: 0.80-1.17). There was a slight decrease in M8 metabolite (AUC0-12 ratio, 0.87; 95% CI: 0.68-1.11) but this was not significant. No serious adverse events occurred through the study period.
  
  
  CONCLUSIONS
  Nelfinavir does not require dose adjustment when coadministered with tenofovir and appears to be well-tolerated by HIV-infected patients.
authors.affiliation: Therapia GmbH, Berlin, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Kruse
authors.forename: Stefan
authors.initials: S
authors.lastname: Esser
authors.forename: Hartmut
authors.initials: H
authors.lastname: Stocker
authors.forename: Antje
authors.initials: A
authors.lastname: Breske
authors.forename: Andreas
authors.initials: A
authors.lastname: Koerber
authors.forename: Maija
authors.initials: M
authors.lastname: Kopperman
authors.forename: Heidi
authors.initials: H
authors.lastname: Wiehler
authors.forename: Birgit
authors.initials: B
authors.lastname: Ross
authors.forename: Christiane
authors.initials: C
authors.lastname: Möcklinghoff
authors.forename: Andrew
authors.initials: A
authors.lastname: Hill
authors.forename: Mark
authors.initials: M
authors.lastname: Becker
authors.forename: Michael
authors.initials: M
authors.lastname: Kurowski
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D019888:Nelfinavir / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D063065:Organophosphonates / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000068698:Tenofovir; D013997:Time Factors
chemical_list: D017320:HIV Protease Inhibitors; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; C495123:hydroxy-t-butylamidenelfinavir; D000068698:Tenofovir; D019888:Nelfinavir; D000225:Adenine