PERTEMUAN 2. Kompartemen 1 Terbuka
PERTEMUAN 2. Kompartemen 1 Terbuka
PERTEMUAN 2. Kompartemen 1 Terbuka
DAN
FARMAKOKINETIKA
Model Kompartemen
Volume Distribusi
Klirens
AUC
Diskusi
Time
3/24/2018 IIK MP BALI 4
Kompartemen Satu Terbuka
D K t
C e
Vd
Drug Conc (C)
C= concentration
D= dose
Vd: Volume of distribution
K: elimination rate constant
t: time
Time
Time
kt 0
Log Cp = log C
2,3 p
dose DB 0
Vd
initial conc. Cp0
12
Volume Distribusi
4. Estimate Vd:
dose DB 0
Vd
initial conc. Cp0
13
Volume Distribusi
6.6
Log (Conc)
6.4
6.2
5.8
0 1 2 3 4 5 6
Time
14
Volume Distribusi
6.6
Log (Conc)
6.4
6.2
5.8
0 1 2 3 4 5 6
Time
15
Volume Distribusi
6.8
6.6
Log (Conc)
6.4
C0
6.2
5.8
0 1 2 3 4 5 6
Time
16
Volume Distribusi
7
4-Estimate Vd
dose DB 0
6.8
Vd
6.6
initial conc. Cp0
Log (Conc)
6.4
Log(C0)
6.2
5.8
0 1 2 3 4 5 6
Time
17
Konstanta Eliminasi
6.8
1- Plot log(C) vs. time
6.7
6.6
Log (Conc)
6.5
6.4
6.3
6.2
6.1
6
0 1 2 3 4 5 6
Time
20
Konstanta Eliminasi
6.8
2- Plot the best-fit line
6.7
6.6
Log (Conc)
6.5
6.4
6.3
6.2
6.1
6
0 1 2 3 4 5 6
Time
21
Konstanta Eliminasi
6.7
log( C1 ) log( C2 )
Slope
t1 t 2
6.6
Log (Conc)
6.5
6.4
6.3
(Log(C1), t1)
6.2
6.1
(Log(C2), t2)
6
0 1 2 3 4 5 6
Time
22
Konstanta Eliminasi
4- Estimate K
6.8
6.7
K Slope 2.303
6.6
Log (Conc)
6.5
6.4
6.3
6.2
6.1
6
0 1 2 3 4 5 6
Time
23
T ½ Eliminasi
24
T ½ Eliminasi
• Two methods:
– From the value of K: 0.693
t1/ 2
K
25
Klirens (Cl)
26
Klirens (Cl)
27
Klirens (Cl)
28
Klirens (Cl)
29
Klirens (Cl)
• Pendekatan Massa
Dosis = 100 mg
Jumlah tereliminasi/menit
Volume cairan = 10 ml
= 10 mg/menit
Kons. = 10 mg/ml
• Pendekatan Fraksi
Dosis = 100 mg Fraksi tereliminasi/menit
Volume cairan = 10 ml = 1 mg/menit
Kons. = 10 mg/ml = 1/10 per menit
dose
Cl
AUC
where AUC is the area under the concentration curve
(it will be discussed next slide)
32
Klirens (Cl)
Cl K Vd
33
Area Under the Cons. (AUC)
• Two methods:
– Model dependent: can be used only for one
compartment IV bolus
– Model independent: Can be used for any drug
with any route of administration
34
Area Under the Cons. (AUC)
Dose C0
AUC
K Vd K
35
Area Under the Cons. (AUC)
1200
AUC calculation: Model independent
1000
800
600
400
200
0
0 2 4 6 8 10 12
36
Area Under the Cons. (AUC)
1200
AUC calculation: Model independent
1000 1- Divide the area into different parts
based on the observed concentration
800 points (parts 1-5)
600
400 1
200
2
3
4 5
0
0 2 4 6 8 10 12
37
Area Under the Cons. (AUC)
1000
2- Calculate the area for each part of the
parts 1,2,3 and 4 (until the last observed
800 concentration) using trapezoidal rule
600
400 1
200
2
3
4 5
0
0 2 4 6 8 10 12
38
Area Under the Cons. (AUC)
Trapezoidal rule
C1
C 2 C1
area (t 2 t1 )
C2 2
where C = concentration
t = time
t1 t2
39
Area Under the Cons. (AUC)
40
Area Under the Cons. (AUC)
1200
AUC calculation: Model independent
1000
4- The total AUC (from zero to infinity) is the sum
of the areas of parts: 1,2,3,4, and 5
600
400 1
200
2
3
4 5
0
0 2 4 6 8 10 12
41
DISKUSI 1
t (jam) C ( microgram/mL)
2 1,2
5 0,3
kt 0 0,693
Log Cp = log C t 1/2 =
2,3 p k
Dosis 300mg
a. Vd = 35,7 L
Cp0 8,4mg / L
C. (1) Mendekati 10 x T ½
t = 10(4) = 40 ja,
(2) Cp0 = 8,4 mcg/mL
dengan 0,1% obat tertinggal
Cp = 0,001 (8,4 mcg/mL) = 0,0084 mcg/mL
k= 0,173 jam-1
log 0,0084 = 0,713t log 8,4
t = 39,9 jam 2,3
t = 12,3 jam