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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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