The steady-state pharmacokinetics of nelfinavir in combination with tenofovir in HIV-infected patients.
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.
Kruse
Guido
G
Therapia GmbH, Berlin, Germany.
Esser
Stefan
S
Stocker
Hartmut
H
Breske
Antje
A
Koerber
Andreas
A
Kopperman
Maija
M
Wiehler
Heidi
H
Ross
Birgit
B
Möcklinghoff
Christiane
C
Hill
Andrew
A
Becker
Mark
M
Kurowski
Michael
M
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
D017320:HIV Protease Inhibitors; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; C495123:hydroxy-t-butylamidenelfinavir; D000068698:Tenofovir; D019888:Nelfinavir; D000225:Adenine