Supplemental Table 1. Intraocular pharmacokinetic (PK) properties of anti-vascular endothelial growth factor (VEGF) after intravitreal injection and methods used for
PK analyses in the literature
Percent
recovery
data
Tissue preparation
Curve
None
Not necessary (in
vivo imaging)
0.5mg/0.
05 mL
2phase
Not available
None
Aqueous humor was
obtained
by
paracentesis, stored
at
-80°C,
and
defrosted
Not mentioned in
details
0.5mg /
0.05 mL
1phase
66.1 µg/mL (1 d)
in aqueous humor
625 µg
1phase
Drugs
Author (Year)
Species
Assay
Ranibizuma
b
Christoforidis
et al. (2013)
Rabbit
Krohne et al.
(2012)
Human
Radioacti
ve
emission
ELISA
Gaudreault et
al. (2007)
Rabbit
ELISA
None
Gaudreault et
al. (2005)
Monke
y
ELISA
Assay
performan
ce:
99109% for
the
vitreous
humor,
83-99%
for
the
retina
Retinal tissues were
dissected into two
layers with Ames
solution
Not mentioned in
details
for
the
vitreous
and
aqueous humor
0.5 or 2
mg
Bakri et
(2007)
Rabbit
ELISA
None
Rabbit
ELISA
None
Frozen
vitreous
samples
were
solubilized in 1%
BSA
and
centrifuged.
Supernatant
was
used for the assay.
Frozen
aqueous
humor : defrosted
Vitreous
sample:
same as done by
Bakri (2009) et al.
Ours
al.
Maximum vitreous
concentration
(time)
Injection
dose
Half-life in
nonvitrectomiz
ed eyes
2.81 days
Half-life in
vitrectomiz
ed eyes
Tissues
2.13 days
1.79 days*
Vitreous
7.19 days
(aqueous)
Not
available
Aqueous
humor
1280 µg/mL (1 h)
2.9 days
Not
available
1phase
169 µg/mL
2.63 days
Not
available
Vitreous,
aqueous
humor,
serum
Vitreous,
aqueous
humor,
retina,
serum
0.5 mg /
0.05 mL
1phase
162
2.88 days
Not
available
Vitreous,
aqueous
humor,
serum
0.25 mg /
0.025mL
2phase
118.01
2.75 days
2.51 days
Vitreous,
aqueous
humor,
retina
for 0.5 mg (0.25 d)
612 µg/mL
for 2 mg (1 d)
µg/mL (1 d)
7.08
in
vitrectomized eye
91.61
±
9.76
µg/mL
in non-
µg/mL
±
Bevacizuma
b
Ahn (2013)
Rabbit
ELISA
None
Christoforidis
et al. (2013)
Rabbit
None
Kakinoki
(2012)
Monke
y
Radioacti
ve
emission
ELISA
Sinapis (2011)
Rabbit
ELISA
None
Meyer (2011)
Human
ELISA
None
Miyake (2010)
Monke
y
ELISA
None
Nomoto
(2009)
Rabbit
ELISA
None
None
Retina
sample:
homogenized
as
done by Nomoto
(2009) et al.
Frozen vitreous and
aqueous
humor
were separated and
solubilized in 1%
BSA
Not necessary (in
vivo imaging)
vitrectomized
(1h)
eye
1.25 mg
/0.05 mL
2phase
967.27 mg/mL in
vitrectomized eye
1021.54 mg/mL in
non-vitrectomized eye
(1h)
7.06
days
Vitreous,
aqueous
humor,
1.25mg /
0.05 mL
2phase
Not available
4.22 days
2.30 days
2.08 days*
Vitreous
Aqueous
humor
samples
were
obtained
by
paracentesis, stored
at
-80°C,
and
defrosted.
Vitreous
and
aqueous
humor
samples
were
obtained by tapping,
stored at -80°C, and
defrosted.
1.25mg /
0.05 mL
Not
menti
oned
Not available
2.8 days
1.5 days*
Aqueous
humor,
serum
1.25mg /
0.05 mL
Not
menti
oned
406.25 μg/ml (1 d)
6.61, 6.51,
and
5.87
days
for
the vitreous,
aqueous
humor, and
serum,
respectively
Not
available
Vitreous,
aqueous
humor,
serum
Aqueous
humor
samples
were
obtained
by
paracentesis, stored
at
-80°C,
and
defrosted.
Aqueous
humor
samples
were
obtained
by
paracentesis, stored
at
-80°C,
and
defrosted.
Iris/ciliary
body,
vitreous,
and
retina/choroid were
separated
and
homogenized
1.5mg or
3.0 mg
1phase
Not available
7.85 days
(1.5mg)
11.69 days
(3.0mg)
Not
available
Aqueous
humor
1.25mg /
0.05 mL
1phase
Not available
2.8 days
Not
available
Aqueous
humor,
serum
1.25mg /
0.05 mL
Not
menti
oned
59.7 µg/mL (1 w)
Not
available
Not
available
Iris/ciliar
y body,
vitreous,
retina/ch
oroid,
days
6.99
Zhu (2008)
Human
ELISA
None
Vitreous
samples
were
centrifuged
and supernatant was
used for the assay.
1.25mg /
0.05 mL
2phase
165 μg/ml (2 d)
Krohne (2008)
Human
ELISA
None
1.5 mg
1phase
Bakri (2007)
Rabbit
ELISA
None
Aqueous humor was
obtained
by
paracentesis, stored
at
-80°C,
and
defrosted.
Frozen
vitreous
samples
were
solubilized in 1%
BSA
and
centrifuged.
Supernatant
was
used for the assay.
1.25 mg
/0.05 mL
1phase
BSA = bovine serum albumin; d=day(s); h = hour; w = week
* lensectomy also performed
plasma
Vitreous
Not
available
33.3 μg/ml (1 d)
0.5
days
(initial),
6.7
days
(terminal)
9.82 days
Not
available
Aqueous
humor
400 µg/mL (1 d)
4.32 days
Not
available
Vitreous,
aqueous
humor,
serum