| |
The Addition of a Second Protease Inhibitor Eliminates Amprenavir-Efavirenz Drug Interactions and Increases Plasma Amprenavir Concentrations S. PISCITELLI*, C. BECHTEL, B. SADLER, J. FALLOON, and the Intramural AIDS Program.
NIH, Bethesda, MD; and Glaxo Wellcome, Res. Triagle Park, NC
Background: Efavirenz (EFV) significantly decreases the AUC of
amprenavir (APV). The addition of a second PI to prevent this reduction
was evaluated.
Methods: 19 PI-experienced HIV+ patients with plasma HIV RNA >
500 were enrolled into 3 treatment groups: (1) APV 1200 mg po BID, ritonavir
(RTV) 200 mg po BID + EFV 600 mg po QD (n = 6); (2) APV 1200 mg po BID,
RTV 500 mg po BID + EFV 600 mg po QD (n = 4); and (3) APV 1200 mg po BID,
nelfinavir (NFV) 1250 mg po BID + EFV 600 mg po QD (n = 9). Sampling for
APV concentrations was performed at steady-state on APV alone (groups
I & 2) and with dual Pls and after the addition of EFV (all groups).
Results: RTV increased the AUC of APV 2.5-fold and the Cmin
by over 400% (Table; meanąSD). No differences were noted between the low-
and high-dose RTV regimens. Similarly, NFV increased APV AUC by 1.6-fold
and Cmin by 200%. The addition of EFV to the dual-PI regimens did not
alter APV PK.
Regimens were well tolerated although more diarrhea occurred in the NFV
group.
Conclusions: The addition of RTV or NFV markedly increased APV
levels, and these increased levels are unaffected by concomitant EFV.
These data suggest that a once-daily regimen of RTV and APV will be effective.
Key Words: amprenavir, efavirenz, ritonavir
|
