1. Intravenous infusion allows for precise control of drug concentrations in the body and eliminates large fluctuations in Cmax and Cmin. Drugs given by constant IV infusion will reach a steady state concentration (Css) when the rate of drug entry equals the rate of drug elimination. 2. For a one-compartment model drug given by IV infusion, the steady state concentration (Css) can be calculated from the infusion rate (R), volume of distribution (Vd), and elimination rate constant (k). 3. A loading dose (DL) may be given by IV bolus at the start of an infusion to quickly achieve the target Css. The amount of the loading dose can be calculated from the infusion

1. FARMAKOKINETIKA DOSIS GANDA
( III )

2. INFUSI - INTRAVENA
INTRAVENA INTRAVENA BOLUS
INTRAVENA LAMBAT – LAJU TETAP
INFUSI INTRAVENA
- PENGENDALIAN TEPAT Cp ~ kebutuhan pasien
- HILANGKAN FLUKTUASI YANG BESAR
CMAKS -- CMIN
Ex. Oksitosin, heparin, aminofilin, cairan elektrolit, nutrient

3. Fig. 5-1. Plasma level-time curve for constant IV infusion
Pada keadaan tunak
laju masukan obat = laju obat keluar
(laju infusi) (laju eliminasi)
dc/dt = 0

4. OBAT – MODEL KOMPARTEMEN SATU
B
B
kD
R
dt
dD


 
kt
D
e
k
V
R
Cp 

 1
  Cl
R
k
V
R
e
k
V
R
Cp
D
D



 

1
Perubahan jumlah obat dalam tubuh pada berbagai waktu
Integrasi persamaan di atas dan substitusi DB = CpVD
Infusi berlanjut t = ~  e-kt mendekati nol
DB = jumlah obat dalam tubuh
R = laju infusi – order nol
k = tetapan laju eliminasi – order satu
CSS

5. ?? LAJU INFUSI  CSS
tSS
Fig. 5-3. Plasma level – time curve for IV infusions given at
rates of R and 2R, respectively

6. CONTOH : Hal. 111 no.1
Suatu antibiotika Vd = 10 L, k = 0,2 jam-1, Css = 10 ug/mL
Berapakah laju infusi untuk mempertahankan konsentrasi tersebut ??
R = Css Vd k
R = (10 ug/m) (10.000 mL) ( 0,2 jam-1)
R = 20 mg/jam
Bila pasien dalam kondisi uremia, tetapan laju eliminasi menurun menjadi 0,1 jam-1
Laju infusi yang baru :
R = (10 ug/m) (10.000 mL) ( 0,1 jam-1)
R = 10 mg/jam

7. INFUSI INTRAVENA  ClT, k, t1/2
Css
R
Cl
Css
R
k
Vd
k
Vd
R
C
T
SS



 
 





 








 










Css
Cp
Css
t
k
kt
Css
Cp
Css
e
Css
Css
Cp
e
Css
Cp
maka
k
V
R
Css
karena
e
k
V
R
Cp
kt
kt
D
kt
D
log
3
,
2
3
,
2
log
1
1
Lihat contoh
hal 112 dan 113

8. Fig 5-4. IV Infusion with loading dose DL
DL is given by IV bolus injection at the start of infusion
Cp decline exponentially after DL whereas they increase exponentially
During the infusion. The resulting Cp versus time curve is a straight line
due to the summation of the two curve
DOSIS MUATAN PLUS INFUSI IV:
MODEL KOMPARTEMEN SATU
Apa tujuan DL???

9. DOSIS MUATAN PLUS INFUSI IV:
MODEL KOMPARTEMEN SATU
1 0
2
( )
(1 )
kt kt
L
d
L
kt
d
DOSIS MUATAN D IV BOLUS
INFUSI DENGAN LAJU R
R
C e
C C e e
V
V
D
k
 

 
 

DL = Css Vd
Css . Vd= R/k
DL = R/k
!! Css  C terapetik Css
1 2
(1 )
( )
( )
L
kt
d
kt
d d
kt
L
kt
L
d
kt
L
d
kt
L
d
L
d d
L
d d
D
e
V
D
e
D dan AWAL INFUSI WAKTU SAMA
Cp C C
R
Cp e
V k
R R
Cp e
V k V k
D D
Cp e
V
D
e
V V
D R
Cp
V V k
V






 
  
  
  
   Css

10. Fig. 5-5. IV Infusion with loading doses a, b, and c.
Curve d represents an IV infusion without a loading dose
a  DL > R/k
b  DL = R/k
c  DL < R/k
!! Cara lain perhit DL
DL = Css . Vd

11. Cp – SETELAH INFUSI DIHENTIKAN
t – waktu infusi + post infusi
b – waktu infusi
  )
(
1
.
b
t
k
kb
e
e
k
Vd
R
Cp 




CARA LAIN LIHAT HAL 191
LIHAT LATIHAN SOAL HAL. 118 dst.
INFUSI IV INTERMITTEN HAL 197
PRINSIP SAMA

12. REGIMENTASI DOSIS ORAL GANDA
N – jumlah dosis
- jarak pendosisan
F – fraksi dosis terabsorpsi
t – waktu setelah do ke n




























 





kt
k
nk
t
k
k
nk
e
e
e
e
e
e
ka
k
Vd
D
ka
F
Cp a
a
a




1
1
1
1
)
(
.
. 0
 



T
av
av
D
av
Cl
FD
C
AUC
C
k
V
FD
C
0
~
~
0
~
0
~




13. PADA KEADAAN TUNAK
k
k
k
k
t
e
e
ka
k
Vd
kaFD
C
e
e
Vd
FD
C
e
e
e
e
ka
k
Vd
D
ka
F
C
a
a
maks
k
k
kt
k
maks
t
k
k
kt
k
p
p
a
a
log
3
,
2
1
1
)
(
1
1
1
1
1
1
)
(
.
.
0
~
min
0
~
0
~






















































