Digoxin

A. KINETIC PARAMETERS
Bioavailability (F):
Protein Binding:
Volume of
Distribution (Vd):

0.70 tablet; 0.80 liquid

25%
7.5L/kg; (CrCl<10mL/min = 5.0L/kg)
Cardiac tissue conc. 15-30 x Plasma
conc.
Distribution time: 8 hours; increased in CHF
Half-Life (t):
36 hours; 4-6 days in renal failure
Therapeutic range: 1-2.5 nmol/L (0.5-2.0 ng/mL)
No maximum in atrial fib if tolerated
DISEASE STATE/
CONDITION

HALF-LIFE

VOLUME OF
DISTRIBUTION

Adult, normal
renal function

36 hours or 1.5 days

7 L/kg
(range: 2448 hours) (range: 59 L/kg)

Usual dose 250 g/d (range:

125500 g/d) resulting in
total body stores of 812 g/kg
for heart failure or 1315 g/kg
for atrial brillaton. Digoxin
is eliminated ~75%
unchanged renally/~25%
nonrenally.

Adult, renal failure

120 hours or 5 days

Renal failure patients have

decreased digoxin clearance
and volume of distribution. As
a result, half-life is not as long
as might be expected [t1/2 =
(0.693V) / Cl]. Digoxin total
body stores decrease to
610 g/kg because of reduced
volume of distribution.

COMMENT

4.5 L/kg
V=

226 +

298 CrCl

( Wt / 70)
where V is digoxin
volume of distribution in
L/70 kg, Wt is body
weight in kg (use ideal
body weight if >30%
overweight) and CrCl is
creatinine clearance
in mL/min.

Moderate/severe
heart failure

See comments

7 L/kg

Heart failure patients (NYHA

IIIIV) have decreased cardiac output, which causes
decreased liver blood ow
and digoxin hepatic clearance. In patients with good
renal function (creatinine
clearance >80 mL/min), the
effect on digoxin total clearance is negligable. But in
patients with poor renal function, (creatinine clearance
<30 mL/min) nonrenal clearance is a primary elimination
pathway.

Obesity (>30% over

IBW) with normal
renal function

36 hours or 1.5 days

7 L/kg IBW

Digoxin does not distribute to

adipose tissue, so volume of
distribution calculations should
be conducted with ideal body
weight (IBW).

Hyperthyroidism
with normal renal
function

24 hours or 1 day

7 L/kg

Hyperthyroid patients are

hypermetabolic and have
higher digoxin renal and
nonrenal clearances.

Farmakodinamik/Farmakokinetik :

Onset of action (waktu onset) : oral : 1-2 jam; IV : 5-30 menit

Peak effect (waktu efek puncak) : oral : 2-8 jam; IV : 1-4 jam
Durasi : dewasa : 3-4 hari pada kedua sediaanAbsorpsi : melalui difusi pasif pada usus
halus bagian atas, makanan dapat menyebabkanabsorpsi mengalami penundaan (delay),
tetapi tidak mempengaruhi jumlah yang diabsorpsi.Distribusi :
Fungsi ginjal normal : 6-7 L/kg
Gagal ginjal kronik : 4-6 L/kg
Anak-anak : 16 L/kg
Dewasa : 7 L/kg menurun bila terdapat gangguan ginjal
Ikatan obat dengan protein (protein binding) : 30%Metabolisme : melalui sequential
sugar hydrolysis dalam lambung atau melalui reduksi cincinlakton oleh bakteri di
intestinal , metabolisme diturunkan dengan adanya gagal jantung kongestif
Bioavailabilitas:
T eliminasi (half-life elimination) berdasarkan umur, fungsi ginjal dan jantung
T eliminasi (half-life elimination): parent drug (obat asal ): 38 jam;
metabolit:digoxigenin: 4 jam ; monodigitoxoside : 3 12 jam
Waktu untuk mencapai kadar puncak, serum: oral ~ 1 jam

Ekskresi : urin (50% hingga 70% dalam bentuk obat yang tidak berubah )
Konsentrasi serum digoksin :
Gagal jantung kongestif : 0,5 -0,8 ng/ml .Aritmia : 0,8-2 ng/ml
Dewasa : < 0,5 ng/ml, kemungkinan menunjukkan underdigitalization, kecuali jika
terdapat hal-hal khusus
Toksik > 2,5 ng/ml\
Bentuk sediaan tablet, eliksir, kapsul cair, dan injeksi.
TOBRAMISIN
Farmakodinamika
Tobramisin tidak jauh berbeda sifatnya dengan gentamisin, termasuk spektrum
antimikrobanya. Karena itu, tobramisin digunakan sebagai pengganti gentamisin.
Aktivitas tobramisin yang superior terhadap P. aeruginosa dibanding gentamisin
menyebabkan obat ini terpilih untuk mengatasi infeksi oleh kuman tersebut. Obat ini
tidak memperlihatkan sinergisme dengan penisilin terhadap enterokok dan inaktif
terhadap mycobacterium. Dibandingkan terhadap gentamisin, terdapat petunjuk bahwa
tobramisin bersifat kurang nefrotoksik, tetapi hal ini belum terbukti secara klinis.
Farmakokinetika
The aminoglycosides are eliminated almost completely (90%) unchanged in the urine
primarily by glomerular ltration (Table 4-1).
These antibiotics are usually given by short-term (1/21 hour) intermittent intravenous
infusions, although they can be given intramuscularly. When aminoglycosides are given
intramuscularly they exhibit very good bioavailability of ~100% and are rapidly absorbed
with maximal concentrations occurring about 1 hour after injection. Exceptions to this
situation are patients who are hypotensive or obese.
Nonobese adults with normal renal function (creatinine clearance >80 mL/min, Table 41) have an average aminoglycoside half-life of 2 hours (range: 1.53 hours), and the
average amino- glycoside volume of distribution is 0.26 L/kg (range: 0.20.3 L/kg) in
this population.

DISEASE STATE/
CONDITION

HALF-LIFE

VOLUME OF
DISTRIBUTION

COMMENT

Adult, normal renal

function

2 hours (range:
1.53 hours)

0.26 L/kg (range:

0.20.3 L/kg)

Usual doses 35 mg/kg/d for

gentamicin, tobramycin,
netilmicin, or 15 mg/kg/d for
amikacin when using conventional
dosing. Usual doses are 57
mg/kg/d for gentamicin or
tobramycin
using extended-interval dosing.

Adult, renal failure

50 hours (range:
3672 hours)

0.26 L/kg

Renal failure patients commonly

have uid imbalances that may
decrease (underhydration) or
increase (overhydration) the volume of distribution and secondarily change half-life.

Burns

1.5 hours

0.26 L/kg

Burn patients commonly have uid

imbalances that may decrease
(underhydration) or increase
(overhydration) the volume of distribution and secondarily change
half-life.

Penicillin therapy
(patients with
creatinine clearance
<30 mL/min)

Variable

0.26 L/kg

Some penicillins (penicillin G,

ampicillin, nafcillin, carbenicillin,
ticarcillin) can bind and inactivate aminoglycosides in vivo
or in vitro (e.g., lab test tubes).

Obesity (>30% over

IBW) with normal
renal function

23 hours

V (in L) =

Aminoglycosides enter the

extracellular uid contained in
adipose tissue requiring a correction factor to estimate volume of
distribution.

Cystic brosis

1.5 hours

0.35 L/kg

Larger volume of distribution and

shorter half-life usually results in
larger daily doses.

Acites/overhydration

Variable

V (in L) =
(0.26
+
(TBW DBW)
DBW)

Aminoglycosides distribute to
excess extracellular uid;
correction equation assumes that
weight gain is due to uid accumulation. Alterations in volume of
distribution can cause secondary
changes in half-life.

0.26
[IBW
+ 0.4
(TBW
IBW)]

Bentuk sediaan Obat ini tersedia sebagai larutan 80 mg/2 ml untu suntikan IM. Untuk
infus Tobramisin dilarutkan dalam Dekstrose 5% atau larutan NaCl isotonis dan diberikan
dalam 30-60 menit. Jangan diberikan lebih dari 10 hari.