Effect of Furosemide on Serum Clearance and Renal Excretion of Digoxin ETSURO
S
1960,
INCE
that
many
diuretics
intoxication, most
available, digoxin
and
treatment
heart gators
of
failure. have
between
stated
its
Furosemide
use
furosemide
is one
with
combined
patients
Although reported
with
and
the
the
in
congestive
several
on
of
currently
employed
investi-
interaction
digoxin,
the
re-
sults are controversial.5-9 The purpose of this study was to clarify the effect of furosemide on serum turnover and renal excretion From
of
of digoxin. the
Department
Constitutional
of
Geriatrics,
Medicine,
-ersity, 4-24-1, Kuhonji,
Institute
Kumamoto
Kumamoto,
Uni-
Volunteer no.
200
of Six
Healthy
Subjects
Methods
ject
characteristics
After
fasting
asked ginning
to
venous
performed on six healthy aged 25 to 35 years. Subare
void urine of the study digoxin
at
weight
Blood
specimens
5,
9,
7,
digoxin
11,
and 15,
15-24
and
subjects
a dose
over
5 were
13,
15,
creatinine were
in
all
the beintra-
of
0.006 at
9
obtained
at
1, 2, 3,
and
24 for
mg/kg
hours
serum
A.M.
after digoxin
measurements. collected
hours
I. were
minutes
Urine
for 0-5,
5-10, 10in Fig.
as illustrated
1. Subjects were allowed water without restriction After
Table
just prior to and received
administration
samples
listed
overnight,
body
study.
Japan.
and
Studies were male volunteers
TABLE Characteristics
FUJIKI. M.D.. HARUO TAKEDA. M.D.. a.d HIDEO FUKUSHIMA. M.D. Kumamoto, Japan
Material
loss
the
diuretics
widely
HIROSHI
digitalis
to
of
potent
is now
have
contribute
potassium.1-3
the
M.D.
authors
because
urinary
of
TSUTSUMI.
to take food throughout
a washout
period
of at
and the least
I and
Doses
of Digozin
and
Furosemide
Age (yra)
Weight (kg)
Body surface
Digoxin
Furosemide
Sex
area (m2)
(mg)
(mg)
1
35
M
80.0
1.98
0.48
80
2
28
M
75.0
1.90
0.44
80
3
28
M
55.0
1.67
0.33
60
4
25
M
63.5
1.76
0.38
70
5
26
M
51.0
1.53
0.31
60
6
27
M
57.0
1.59
0.34
60
The
Journal
of Clinical
Pharmacology
EFFECT
DIGOXIN
OF
FUROSEMIDE
of
0.006mg/kg
I
FUROSENIOC
liii
p.0.
I
I
I
I
I
1400
Fig.
1.
Schedule
900
for
I
I
2400
0900
blood
and
urine
sam-
weeks,
peated
the
same
except
for
furosemide,
5 hours The
digoxin
were
assay amounts
digoxin-free
ported
by was
and by
sera
and
recovery. by a
factory
for
both
digoxin
(Fig.
2);
urine
serum the
kits
then
al.4
A
urine
2 to
40
times
at was
and
lowest
Average
serum digoxin furosemide
observed
For the
always control hours
higher
than
period, (distribution
significant
those
same
study radio-
lot.
observed
except
for phase).
differences
in
at
15
and
24
hours
shown
in
Fig.
3,
the
1979
to creatinine
nificantly
decreased
diuresis
caused
the
15.0 There
24-hour
furosemide.
the
ratio
The
of digoxin
clearance during the
by
±
also period
furosemide
sigof
(Table
III).
Digoxin neys,
is excreted
and
its
mainly
excretion
rate
by
the
kid-
is dependent
on the glomerular filtration rate. So one can speculate that digoxin excretion might be accelerated by high urinary
8 t6
o o z
in
-
0 0
2
the
serum
digoxin
(Table
II).
half-life
4
6
DIGOXIN
the first 5 There were
serum
in
with
clearance
42.4 0.05).
S
1960,
INCE
that
many
diuretics
intoxication, most
available, digoxin
and
treatment
heart gators
of
failure. have
between
stated
its
Furosemide
use
furosemide
is one
with
combined
patients
Although reported
with
and
the
the
in
congestive
several
on
of
currently
employed
investi-
interaction
digoxin,
the
re-
sults are controversial.5-9 The purpose of this study was to clarify the effect of furosemide on serum turnover and renal excretion From
of
of digoxin. the
Department
Constitutional
of
Geriatrics,
Medicine,
-ersity, 4-24-1, Kuhonji,
Institute
Kumamoto
Kumamoto,
Uni-
Volunteer no.
200
of Six
Healthy
Subjects
Methods
ject
characteristics
After
fasting
asked ginning
to
venous
performed on six healthy aged 25 to 35 years. Subare
void urine of the study digoxin
at
weight
Blood
specimens
5,
9,
7,
digoxin
11,
and 15,
15-24
and
subjects
a dose
over
5 were
13,
15,
creatinine were
in
all
the beintra-
of
0.006 at
9
obtained
at
1, 2, 3,
and
24 for
mg/kg
hours
serum
A.M.
after digoxin
measurements. collected
hours
I. were
minutes
Urine
for 0-5,
5-10, 10in Fig.
as illustrated
1. Subjects were allowed water without restriction After
Table
just prior to and received
administration
samples
listed
overnight,
body
study.
Japan.
and
Studies were male volunteers
TABLE Characteristics
FUJIKI. M.D.. HARUO TAKEDA. M.D.. a.d HIDEO FUKUSHIMA. M.D. Kumamoto, Japan
Material
loss
the
diuretics
widely
HIROSHI
digitalis
to
of
potent
is now
have
contribute
potassium.1-3
the
M.D.
authors
because
urinary
of
TSUTSUMI.
to take food throughout
a washout
period
of at
and the least
I and
Doses
of Digozin
and
Furosemide
Age (yra)
Weight (kg)
Body surface
Digoxin
Furosemide
Sex
area (m2)
(mg)
(mg)
1
35
M
80.0
1.98
0.48
80
2
28
M
75.0
1.90
0.44
80
3
28
M
55.0
1.67
0.33
60
4
25
M
63.5
1.76
0.38
70
5
26
M
51.0
1.53
0.31
60
6
27
M
57.0
1.59
0.34
60
The
Journal
of Clinical
Pharmacology
EFFECT
DIGOXIN
OF
FUROSEMIDE
of
0.006mg/kg
I
FUROSENIOC
liii
p.0.
I
I
I
I
I
1400
Fig.
1.
Schedule
900
for
I
I
2400
0900
blood
and
urine
sam-
weeks,
peated
the
same
except
for
furosemide,
5 hours The
digoxin
were
assay amounts
digoxin-free
ported
by was
and by
sera
and
recovery. by a
factory
for
both
digoxin
(Fig.
2);
urine
serum the
kits
then
al.4
A
urine
2 to
40
times
at was
and
lowest
Average
serum digoxin furosemide
observed
For the
always control hours
higher
than
period, (distribution
significant
those
same
study radio-
lot.
observed
except
for phase).
differences
in
at
15
and
24
hours
shown
in
Fig.
3,
the
1979
to creatinine
nificantly
decreased
diuresis
caused
the
15.0 There
24-hour
furosemide.
the
ratio
The
of digoxin
clearance during the
by
±
also period
furosemide
sigof
(Table
III).
Digoxin neys,
is excreted
and
its
mainly
excretion
rate
by
the
kid-
is dependent
on the glomerular filtration rate. So one can speculate that digoxin excretion might be accelerated by high urinary
8 t6
o o z
in
-
0 0
2
the
serum
digoxin
(Table
II).
half-life
4
6
DIGOXIN
the first 5 There were
serum
in
with
clearance
42.4 0.05).
