Acid-reducing
Agents Do Not
Alter the Pharmacokinetics
of Lopinavir/Ritonavir Tablet By
Ronald Baker,
PhD PI
adverse events
are responsible
for the discontinuation
or switching
of therapy
in up to half
of patients
on initial HAART
regimens.
A consequence
of this has
been increasing
HIV patient
use of prescription
or over-the-counter
(OTC) acid-reducing
agents (ARAs)
without physician
input or oversight.
These include
proton
pump inhibitors
[PPIs]
(eg,
omeprazole)
and H2
antagonists
(eg,
ranitidine).
Because
many PIs need
an acid environment
for appropriate
drug absorption
and dissolution,
the use of these
acid-reducing
agents decreases
the bioavailability
of some PIs.
The
impact of these
acid-reducing
agents on lopinavir/ritonavir
(LPV/r) [Kaletra]
in any formulation
has not been
formally studied,
and the influence
of decreased
stomach acidity
on drug bioavailability
from a novel
melt-extrusion
LPV/r tablet
is unknown.
To
address this
issue, researchers
at Abbott Laboratories
evaluated the
effect of omeprazole
and ranitidine
on the pharmacokinetics
of LPV/r tablet
administered
once or twice
daily and atazanavir
(ATV) [Reyataz]
boosted by ritonavir
(RTV) capsule.
Seventy-one
71 healthy HIV
positive adults
were randomized
to receive LPV/r
tablets 400/100
mg twice daily
or 800/200 mg
once daily or
RTV capsule
100 mg + ATV
300 mg once
daily from study
day 1 to 15,
approximately
30 minutes after
a meal.
Either
omeprazole
40 mg once daily
was administered
1 hour before
breakfast on
study days 11
to 15 or ranitidine
150 mg was administered
1 hour before
breakfast on
study day 11.
Serial blood
samples were
collected during
a dosing interval
(for 12 or 24
hours after
dosing) on study
days 10, 11,
and 15.
The
pharmacokinetic
parameters of
LPV, RTV, and
ATV were compared
with and without
omeprazole
or ranitidine. Results
The
comparison of
LPV and RTV
pharmacokinetics
with and without
omeprazole
or ranitidine
for LPV/r is
shown in the
table. As previously
shown, ATV levels
were significantly
decreased, but
RTV levels were
unchanged with
administration
of ATV + RTV
with omeprazole
or ranitidine.
|
|
PK
Parameter |
Relative
Bioavailability |
|
Point
Estimate |
90%CI |
|
LPV/r
twice daily
+ omeprazole
vs
LPV/r
twice daily |
LPV
Cmax |
1.08 |
0.99
– 1.17 |
|
LPV
AUC12 |
1.07 |
0.99
– 1.15 |
|
RTV
Cmax |
1.11 |
0.95
– 1.30 |
|
RTV
AUC12 |
1.07 |
0.98
– 1.17 |
|
LPV/r
once daily +
omeprazole
vs
LPV/r
once daily |
LPV
Cmax |
0.94 |
0.88
– 1.00 |
|
LPV
AUC24 |
0.92 |
0.86
– 0.99 |
|
RTV
Cmax |
0.90 |
0.79
– 1.03 |
|
RTV
AUC24 |
0.92 |
0.84
– 1.01 |
|
LPV/r
twice daily
+ ranitidine
vs LPV/r
twice daily |
LPV
Cmax |
0.98 |
0.95
– 1.02 |
|
LPV
AUC12 |
0.98 |
0.94
– 1.01 |
|
RTV
Cmax |
0.94 |
0.84
– 1.05 |
|
RTV
AUC12 |
0.94 |
0.87
– 1.01 |
|
LPV/r
once daily +
ranitidine
vs
LPV/r once daily |
LPV
Cmax |
0.98 |
0.95
– 1.01 |
|
LPV
AUC24 |
0.96 |
0.90
– 1.02 |
|
RTV
Cmax |
0.88 |
0.77
– 1.01 |
|
RTV
AUC24 |
0.92 |
0.83
– 1.02 |
Based
on these findings,
the authors
conclude, “Acid-reducing
agents do not
significantly
alter LPV or
RTV exposure
after co-administration
with LPV/r 400/100
mg twice daily
or 800/200 mg
once daily or
with RTV 100
mg twice daily.” “Drug
bioavailability
from a novel
melt-extrusion
LPV/r tablet
is not altered
by acid-reducing
agents.” 02/21/06 Reference
C
Klein and others.
Lack
of Effect of
Acid-reducing
Agents on the
Pharmacokinetics
of Lopinavir/Ritonavir
Tablet.
13th
Conference on
Retroviruses
and Opportunistic
Infections.
February
5-8, 2006, Denver,
CO.
Abstract 578.
| 
