Ritonavir-boosted Darunavir Does Not Produce Significant Pharmacokinetic Changes
when Coadministered with Ranitidine or Omeprazole
Darunavir
(Prezista), formerly called TMC114, is a nonpeptidic HIV protease inhibitor
(PI). On June 23, 2006 the US Food and Drug Administration (FDA) granted "fast
track" (accelerated) approval to darunavir for use in combination with ritonavir
and other antiretroviral agents for the treatment of HIV infection in adults.
Darunavir is indicated
for the treatment of HIV infection in antiretroviral treatment-experienced adults,
such as those infected with HIV-1 strains resistant to more than one PI.
Darunavir
is a second generation PI that is highly active in vitro against both wild-type
and PI-resistant HIV. The drug is regarded as a potential substitute for PIs currently
used in the treatment of HIV. Darunavir is FDA-approved in combination with low-dose
(100mg) ritonavir as a pharmacokinetic enhancer.
It is widely known that
the absorption of the HIV protease inhibitors may be significantly decreased when
they are used together with agents that interfere with the body's production of
stomach acid and increase gastric pH.
Researchers at Tibotec conducted
the current study to evaluate the potential effect of ranitidine and omeprazole
on the pharmacokinetics of darunavir in 16 healthy, HIV negative volunteers.
The
volunteers who completed the study received darunavir/ritonavir (TMC114/r), TMC/r
plus ranitidine and TMC/r plus omeprazole in three different sessions.
The
volunteers received treatment for 4 days plus an additional morning dose on Day
5.
Results
•
No significant changes in TMC114 pharmacokinetic parameters were noted during
co-administration of TMC114/r with either ranitidine or omeprazole, when compared
with TMC114/r alone.
•
Treatment regimens
were generally well tolerated and no serious adverse events were reported.
The
authors write in conclusion, "Co-administration of TMC114/r and ranitidine
or omeprazole was well tolerated by the volunteers. Ranitidine and omeprazole
did not have a significant influence on TMC114 pharmacokinetics. No dose adjustments
are required when TMC114/r is co-administered with omeprazole or ranitidine."
Tibotec
Inc. Yardley, PA, USA; Tibotec BVBA, Mechelen, Belgium.
01/12/07
Reference
V J Sekar, E Lefebvre, E De Paepe, and others. Pharmacokinetic
interaction between TMC114/r and omeprazole or ranitidine in HIV-negative
healthy volunteers. Antimicrobial Agents and Chemotherapy. Published online
ahead of print on January 8, 2007. doi:10.1128/AAC.01203-06.
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