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Maraviroc
API |
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Haorui supplies high quality Maraviroc API produced by our
GMP facility that has been successfully inspected by the
FDA.
We offer
competitive prices and support our products with reliable technical and
regulatory services. Maraviroc API is available from R&D to
commercial quantities. Please contact us for more details. |
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The following
information is provided for general information purposes
ONLY. |
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What is Maraviroc? |
Maraviroc is a chemokine receptor antagonist.
It is designed to prevent HIV infection of CD4 T-cells by
blocking the CCR5 receptor. When the CCR5 receptor is
unavailable, ®R5-tropic' HIV cannot engage with a CD4 T-cell
to infect the cell. This variant of the virus is common in
earlier HIV infection, while ®X4-tropic' viruses adapted to
use the CXCR4 receptor gradually become dominant later in
disease.
Maraviroc is being developed by Pfizer. During development,
it was called UK-427,857. It is the first agent in its class
to be tested in people with HIV infection.
Preliminary results of a phase I study were presented in
2003. Twenty-four HIV-positive patients with R5-tropic virus
were randomised to receive maraviroc at 25mg once daily or
100mg twice daily, or placebo for 14 days as monotherapy.
Steady state drug levels were reached within seven days,
with higher drug levels in patients who had fasted. By day
14, the 100mg group had experienced a viral load decline of
1.4 log10, compared with 0.4 log10 in the 25mg group. The
drug was well tolerated, and viral load did not rebound
immediately upon cessation of the drug, indicating that a
proportion of receptors remain blocked for some time.
A similar study comparing a range of doses also showed viral
load reductions of more than 1 log10 at doses above 100mg
once or twice daily, with no effect of food on the drug's
antiviral efficacy[2]. A placebo-controlled safety study of
maraviroc 100 and 300mg twice daily in 54 HIV-negative
adults showed no effect on lipids, blood chemistry or the
activity of the heart. The dose of 300mg twice a day seems
to be the most promising choice for future development,
although 300 and 600mg once a day are also being
investigated in current trials.
Since maraviroc binds to the CCR5 co-receptor, there has
been some concern that its use in patients with R5-tropic
HIV might stimulate a conversion to HIV that uses the
alternative CXCR4 co-receptor. In addition to causing
resistance to maraviroc, this may be linked to more rapid
disease progression. In a study of 62 patients with
R5-tropic virus given maraviroc alone for ten days, only two
patient's virus became X4-tropic, before reverting to use of
the CCR5 co-receptor after treatment was stopped. Subsequent
analysis revealed that the X4-tropic virus in these two
patients emerged from the patients' stores of the virus,
rather than due to the R5-tropic virus mutating into
X4-tropic as a result of the presence of maraviroc[4].
However, investigators plan to keep track of the co-receptor
use of HIV in longer-term trials of the drug.
A phase IIb / III study of once- and twice-daily maraviroc
in combination with AZT (zidovudine, Retrovir) and 3TC (lamivudine,
Epivir) in patients who have never taken anti-HIV drugs
before is currently underway. This study is comparing three
doses of maraviroc to efavirenz (Sustiva). All of the
patients in this study are thought to be susceptible to
maraviroc after a test for R5-tropic virus.
In December 2005, one hepatitis C co-infected patient in
this trial developed liver toxicity after five day's
treatment with maraviroc. This was so severe that the
patient required a liver transplant. However, the study's
data and safety monitoring board judged this to be due to
other medications the patient was taking to prevent
tuberculosis and Pneumocystis pneumonia (PCP), although they
could not rule out a contribution of maraviroc. Although
only one case out almost 1000 patients taking maraviroc in
the trial, this finding was of concern since trials of
GlaxoSmithKline's entry inhibitor aplaviroc were stopped in
October 2005 following reports of severe liver toxicities.
A similar study was started in patients who have experience
of HIV treatments. However, the once-daily maraviroc arm of
this study was halted in January 2006, since this arm's
responses were non-inferior to the efavirenz arm.
A third study is testing maraviroc in combination with an
optimised background regimen in 186 highly
treatment-experienced patients who have both R5- and
X4-tropic HIV. Although the trial failed to show a benefit
of once- or twice-daily maraviroc over placebo in terms of
viral load suppression in this group of patients, maraviroc
did bring about an increase in CD4 cell counts. Although the
suppression of R5-tropic HIV led to an increase in the
proportion of patients with X4-tropic virus, this was not
associated with a fall in CD4 cell counts or disease
progression, in contrast to what is observed in HIV-positive
patients with X4-tropic virus.
Maraviroc is a substrate of the CYP3A4 enzyme, and has
potential interactions with other drugs that are broken down
by this enzyme, particularly protease inhibitors. For
example, levels of maraviroc are increased in patients also
taking atazanavir (Reyataz), ritonavir-boosted lopinavir (Kaletra)
and ritonavir (Norvir)-boosted saquinavir (Invirase).
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Disclaimer:
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Information on this page is provided for
general information purposes. You should not make a clinical
treatment decision based on information contained in this
page without consulting other references including the
package insert of the drug, textbooks and where relevant,
expert opinion. We cannot be held responsible for any errors
you make in administering drugs mentioned on this page, nor
for use of any erroneous information contained on this
page. |
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