Background: ATV is a new protease
inhibitor with excellent anti-HIV activity. RIF, an antimicrobial agent, is
a cytochrome P450 (CYP) 3A inducer and may be used
with ATV, a CYP3A substrate. The objective
was to evaluate the PK effect of RIF on ATV with and without RTV.
Methods: Healthy subjects (n=30)
received 400 mg ATV qd in an open-label, randomized
study for 14 days. For the next 14 days,
10 subjects each received (A) 400 mg ATV+150 mg RIF qd;
(B) 600 mg ATV+150 mg RIF qd; or (C) 400 mg ATV+150
mg RIF+100 mg RTV qd. All doses were
administered with a light meal. Serial
blood samples were collected for PK profiles on days 14 and 28.
Results: Geometric mean (CV%) and ratio of the geometric means (90% confidence
intervals, C.I.) for the PK parameters of ATV are shown.
|
Parameter
|
Group
|
|
Ratio
(90% C.I.)
|
|
|
Cmax
(ng/mL)
|
A
B
C
|
|
1.34 (1.14, 1.60)
2.04 (1.76, 2.37)
1.81 (1.51, 2.17)
|
|
AUC (TAU)
(ng·h/mL)
|
A
B
C
|
|
1.15 (0.98,
1.34)
2.09 (1.82,
2.40)
2.91 (2.46,
3.45)
|
|
|
|
|
|
|
|
|
ATV
exposure at 400 mg did not change with RIF (Treatment A), but was 2- to
3-fold higher with Treatments B and C. The geometric mean (CV%) for the AUC of
RIF for treatments A, B, and C were 7693.77 (20.34); (B) 6291.70 (19.66); and
(C) 7386.71 (19.48), respectively, suggesting that the PK of RIF was comparable
across treatments but 2.5 fold higher than literature values for a standard 300-mg
dose. There were no SAEs reported.
Conclusion: ATV may be co-administered
without modification at the standard dose of 400 mg with RIF. RIF dose modification may be
necessary.
