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Pharmacokinetic properties of toceranib phosphate (Palladia, SU11654), a novel tyrosine kinase inhibitor, in laboratory dogs and dogs with mast cell tumors.
[cutaneous mastocytosis]
Toceranib
phosphate
(
Palladia
,
SU
11654
)
,
an
oral
tyrosine-kinase
inhibitor
,
is
under
investigation
for
the
treatment
of
mast
cell
tumors
in
dogs
.
The
pharmacokinetics
of
toceranib
phosphate
has
been
characterized
in
dogs
.
Means
of
the
following
pharmacokinetic
parameters
were
estimated
following
a
1
.
0
mg
/
kg
i
.
v
.
dose
to
laboratory
beagles
:
plasma
clearance
of
1
.
45
L
/
kg
/
h
,
volume
of
distribution
of
29
.
7
L
/
kg
,
and
terminal
half
-life
of
17
.
7
h
.
Following
single
oral
doses
of
3
.
25
mg
/
kg
administered
to
laboratory
beagles
,
mean
C
(
max
)
estimates
ranged
from
68
.
6
ng
/
mL
to
112
ng
/
mL
with
t
(
max
)
ranging
from
5
.
3
h
and
9
.
3
h
postdose
.
Terminal
half
-life
was
estimated
at
31
h
.
Oral
bioavailability
was
76
.
9
%
.
There
were
no
statistically
significant
(
P
>
0
.
05
)
differences
with
any
pharmacokinetic
parameter
due
to
fed
/
fasted
state
or
with
time
during
13
weeks
of
every-other-
day
dosing
at
3
.
25
mg
/
kg
.
Toceranib
concentrations
were
proportional
with
dose
over
the
range
of
2
.
0
to
6
.
0
mg
/
kg
.
The
pharmacokinetics
of
toceranib
in
client-owned
dogs
of
a
variety
of
pure
and
mixed
breeds
with
mast
cell
tumors
was
similar
to
that
in
healthy
laboratory
dogs
.
In
summary
,
toceranib
phosphate
exhibited
moderate
clearance
,
a
high
volume
of
distribution
,
and
a
moderate
elimination
half
-life
.
After
a
single
oral
dose
at
3
.
25
mg
/
kg
,
the
concentration
vs
.
time
curve
showed
broad
,
sustained
exposure
with
measurable
concentrations
for
more
than
48
h
.
These
pharmacokinetic
parameters
support
every-other-
day
administration
of
toceranib
phosphate
at
an
initial
dose
of
3
.
25
mg
/
kg
for
the
treatment
of
mast
cell
tumors
in
dogs
.
Diseases
Validation
Diseases presenting
"is under investigation for the treatment of mast cell tumors in dogs"
symptom
cutaneous mastocytosis
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