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INFUSI INTRAVENA
Oleh : Fransiska M.C., S.Farm., Apt

Objectives
1
2
3

To demonstrate the differences between intravenous

bolus injection with continuous infusion.
To develop the equations of the model based on the
plasma concentration of unchanged drug.
To review the general principles of steady state.
Be able use the integrated equations for drug
concentrations during and after IV infusion
administration; to calculate parameter values and
suitable dosing regimens including IV infusion
alone or infusion/bolus dosage regimens

Remember this .. !!
What profile is it ?
What is the disadvantage of this route of
administration ?

Theory of IV Infusion

One Compartement Model

R
Dose

Zero-order

CENTRAL
(DB ,Vd)

K
First-order

Du

Drug is administered at a selected or calculated constant

rate (R), controlled by :
Flow rate (mL/jam)
Concentration of drug solution (% w/v)
R = mass per unit time (mg/jam)

The elimination of drug from the body (K) follows a firstorder process.
R>K

Rate of Infusion (R)

R
R= K

R> K

Profile of IV Infusion

Term & Parameter

Cl

Renal clearance

Elimination rate contant

Cp

Plasma drug concentration at time t

Css
tss
LD

Plasma drug concentration at steady state

Time to reach Css
Loading dose

Before thatlets try to remember

At Ao.e

Kt

IV
BOLUS

At A0 .e Kt
Cp Cp0 .e

Kt

: Vd

Cp at time t (Cp)
dA
rate of input rate of output
dt
dA
R KA
dt
IV
R
INFUSION
At
1 e kt
K
: Vd
R
Cpt
1 e kt
K .Vd

So, the equation is

R
kt
Cp
1 e
K .Vd

Soal
Hitunglah konsentrasi obat dalam plasma pada
jam pertama setelah dimulainya infus dengan
laju 100 mg/jam apabila diketahui klirens
ginjalnya 1,5 L/jam dan Vd 10 L.
( 9,28 mg/L )

Dengan harga yang sama, hitunglah laju infusi

yang harus diatur untuk mendapatkan
konsentrasi plasma pada jam pertama sebesar
10 mg/L.
R
( 107 mg/jam )

Cp

1 e
K .Vd
kt

Steady State Consentration (Css )

Css = Kadar tunak = Kadar plateu
theraupetic concentration
= kadar yang diinginkan
Css is a condition when :
rate of input = rate of output
No change in plasma
concentration (= 0)
So, the equation is

Css

Vd K

dA
0
dt
R KA 0
R KVd C p 0
R KVd C p
R
Cp
Vd K

Css
Another way .

Concentration at time (t)

R
Cpt
1 e Kt
Vd K

At steady state condition, t >>>

e-Kt becomes negligible ( 0)

R
Css
Vd K

Question????
An antibiotics was given with two different rates
to a patient (Vd = 3 L, K = 0,5/hour).
Rate I
= 15 mg/jam
R
Css
Rate II = 30 mg/jam
Vd K
Calculate the Css ?
Explain the relationship between rate n Css !

If R is increased 2x

Css II
Css I

tss
R increase twice (2x), Css also increase twice (2x)
tss (time to reach Css) doesnt change

Rising phase of the infusion

curve is governed by the
rate of elimination (K)

Height of plateau is
governed by the rate
of infusion (R)

2R
Cp

tss

time

R
Css
Vd K

tss
What about tss ??
What can influence tss value???
Rule: Steady state condition
min 90% Css
Kt
R
Cp
(1 e
)
Vd K

Cp 90% Css

tss

So, tss value depends on t1/2

90% Css 3,32 t

95% Css 4,32 t
99% Css 6,65 t

Question
Suatu antibiotik memp Vd 12L dan K 0,15 jam-1.
Kons tunak yang diinginkan 20g/ml.
berapakah laju infusi yang diperlukan?

JAWAB :
R = Css.Vd.K
= (20g/ml).(12.1000ml).(0,15jam-1)
= 36mg/jam

Question ??
Terdapat 3 obat, A, B, dan C.
A

Laju infus (mg/jam)

10

20

15

Konst. Eliminasi (/jam)

0,5

0,1

0,05

Klirens (L/jam)

20

Pertanyaan :
1. Mana obat yang akan mencapai kondisi steady
state terlama?
2. Mana yang mempunyai kadar tunak tertinggi ?
3. Mana yang punya Vd terbesar ?

LD
LD = Loading Dose = Dosis Muatan
To reach the steady-state levels of a drugs
immediately
Usually given with iv bolus dose as initial LD or LD
given during infusion.
LD = total amount of drugs in the body when steady
state levels reached
LD C ss .Vd

Unit : massa

LD

R
K

R
.Vd
Vd .K

Initial LD
Plasma drugs concentration at time t after LD
injection :

LD Kt
Cp
e
Vd
Plasma drug concentration during infusion

R
Kt
Cp
(1 e )
Vd . K

Total Cp with initial LD

C2

C1

LD=R/K

Total concentration
(Cp) at time t after
combination of
intravenous bolus
(LD) and infusion

= C1 + C 2

LD Kt R
Cp
e
(1 e Kt )
Vd
Vd .K

Can U explain this.?

Question..??
Antibiotik X diberikan dengan laju infusi 60
mg/jam. Diketahui Vd sebesar 25 L dan tetapan
eliminasinya 0,17/jam. Hitunglah :
a. LD untuk mencapai kadar tunak secepatnya.
b. Konsentrasi total obat dlm plasma pada jam
pertama.

LD given during infusion

Reason :The dose given by constant rate
infusion cant reach Css target.
The equation is .

Vd (Css t arg et Css capaian )

LD
S .F
Note : S = The salt form correction factor/salt
value

Salt value / Salt correction factor

Administration of drugs frequently requires that
drug be soluble in an aqueous medium to
facilitate its administration esp. i.v.
For drugs which are insoluble in aqueous
solvent salt form
Drugs

Salt form

Salt value

Theophylline

Aminophylline

0.85

Procainamide

Procainamide HCl 0.87

Phenytoin

Phenytoin Na

0.92

Phenobarbital

Phenobarbital Na

0.90

Lidocaine

Lidocaine HCl

0.87

Salt value
Calculation the LD
Ex: 100 mg theophylline/0,85 (salt value) = 117,64 mg
aminophylline as LD
Therefore, 117,64 mg aminophylline is equivalent to
100 mg theophylline

Calculation of R
10 mg/h theophylline/0,85 (salt value) = 11,764 mg/h
aminophylline for infusion rate
Therefore, 11,764 mg aminophyllin (salt value 0,85) is
equivalent to 10 mg theophylline.

Question ??
Seorang pasien penderita asma (78 kg, 48 tahun)
dg riwayat perokok berat diberi suatu infusi IV pd
laju 0,6 mg/kg jam. Dengan penambahan LD awal
aminofilin iv bolus dosis 6 mg/kg mencapai Css
sebesar 5,8 mg/L. Hal ini ternyata belum
memberikan efek yg maksimal sehingga dokter ingin
meningkatkan Css menjadi 10 mg/L. Bila diketahui
Vd 0,451/kg BB, sebagai farmasis, apa yg bisa
Anda sarankan?
(Aminofilin adalah garam etilendiamin dari teofilin yg
mgd 85% basa teofilin)

How about if Infusion is stopped?

Followed first order

Plasma Concentration after Termination of Infusion

Bila belum tunak

Bagaimana bila
infusi dihentikan
setelah
konsentrasi
tunak tercapai ?

CARA LAIN :

R
Cpt
(1 e Kti )e K (t ti )
Vd .K

ti = duration of infusion
t ti = time after the termination
infusion

Question..??
Diketahui Vd = 25 L; K = 0,17/jam, Infus dengan
laju sebesar 735 mg/jam dijalankan selama
setengah jam, kemudian dihentikan. Hitunglah
Cp setelah 4,5 jam !

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