model 2 kompartemen terbuka intravaskuler
DESCRIPTION
MODEL 2 KOMPARTEMEN TERBUKA INTRAVASKULER. Wahyu Widyaningsih. Model 2 kompartemen terbuka i,.v. V 1 .Cp. V 2 .Cp. k 1-2. k 2-1. ke. Kompartemen sentral(1): organ-organ yg perfusinya cepat. Misal: darah, Hepar, ginjal dan paru Kompartemen perifer (2): Organ dengan - PowerPoint PPT PresentationTRANSCRIPT
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MODEL 2 KOMPARTEMEN MODEL 2 KOMPARTEMEN TERBUKATERBUKA
INTRAVASKULERINTRAVASKULER
MODEL 2 KOMPARTEMEN MODEL 2 KOMPARTEMEN TERBUKATERBUKA
INTRAVASKULERINTRAVASKULER
Wahyu WidyaningsihWahyu Widyaningsih
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Model 2 kompartemen terbuka i,.v
V1.Cp V2.Cpk1-2
k 2-1
keKompartemen sentral(1): organ-organ yg perfusinya cepat. Misal: darah,Hepar, ginjal dan paruKompartemen perifer (2): Organ dengan Perfusi lambat. Misal otot, kulit, lemak dantulang
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SINONIM• kel= k1.0 = k = tetapan kecepatan
eliminasi• V1 = Vc = V sentral = volume
kompartemen sentral• V2 = VT = Volume jaringan
/kompartemen perifer• Cp = C1 = kadar di kompartemen
sentral• CT = C2 = Kadar di kompartemen
perifer
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ASUMSI MODEL:1. Eliminasi terjadi pada kompartemen sentral2. Semua proses kinetik orde pertama
Persamaan matematik:
tt eBeAtCp .. ..)(
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Kurva, α > β
b
a
Log Cp
B
T
teB ..
teA ..
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kurva
b
a
Log Cp
B
T
teB ..
teA ..
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tt eBeAtCp .. ..)( Diintegrasikan:
Dari pers umum jika t>>> maka A.e –α.t semakin kecil, diabaikan, shg pers menjadi:
Monoeksponensial (karakteristik 1 kompartemen i.v) Co.e -α.t
BA
AUC
teBtCp ..)(
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Cara mencari nilai α( tetapan kec distribusi)
• LR t vs ln Cp pada fase eliminasi ln Cp= ln B- β.t (pers 1) --- slope –β
• Dicari Cp’ dengan cara mensubstitusi t pada distribusi pada pers 1.
• Dicari ΔCp = Cp dist – Cp’
• Buat LR t vs ln ΔCp ln Cp (r)=ln A-α.t
• Slope -α (tetapan kecepatan distribusi)
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VOLUME DISTRIBUSI
• Volume semu• Untuk menghitung jumlah obat didalam
tubuh (dari Cp)• Proporsional dg berat badan
• Harga tgt: 1. Kec aliran darah pada jaringan2. Kelarutan obat dlm lemak3. Koefien partisi4. Jenis jaringan5. pH lingkungan6. Ikatan dg material biologis
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Arti harga Vd
Harga Vd (L)
Arti
5 Distribusi sirkulasi sistemik
10-20% (15-
27%BB)
Cairan ekstrasel
40(60%BB)
Seluruh cairan badan
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MACAM VOLUME DISTRIBUSI
1.Volume kompartemen sentral (Vp=V1)
Guna: - menggambarkan perubahan konsentrasi obat (krn cuplikan diambil dari kompartemen sental)
- untuk penentuan kliren (Cl) - petunjuk adanya distribusi obat di
cairan tubuh
BA
Div
Cp
DivVp
0
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2. Vd pada keadaan tunak (obat yg masuk ke komp jaringan= yg keluar dari komp jaringan)
3. Vd yg diekstrapolasikan
4. Vd area Vd.β
1.2
0.k
VpB
DVdeks
Vpk
kkVdss .
2.1
1.22.1
kliren
B
DoVdVdarea .
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RUMUS PARAMETER FARMAKOKINETIKAMODEL 2 KOMPARTEMEN I.V
Rumus umum:
A=intersep fase distribusiB= intersep fase eliminasi
Co= A+B
tt eBeAtCp .. ..)(
)(
)(
)(
)(.
1
1.2
1
1.2
V
kDivB
V
kvDiA
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LANJUTAN RUMUS
BAAUC
t
Cp
BAk
BACp
BAk
693,0
..
..(
)(.
2/1
01.2
0
2
2.1
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LANJUTAN RUMUS
• Ab= jumlah obat di dalam badan
CL
VdAUC
vDiVd
AUC
DCL
area
VIT
.
.
.
CpVdAb .
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Konsentrasi obat dlm plasma seorang penderita yg menerima antibiotik dosis
100mg didapatkan data sbb :
Waktu, menit
Kons. (μg/ml)
2 680,35
5 446,48
10 277,33
20 181,69
Waktu, menit
Kons. (μg/ml)
30 146,28
45 110,28
60 83,43
90 47,80
120 27,38
150 15,68
180 8,98
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Hitung harga parameter farmakokinetikanya!
LANGKAH PENGERJAAN:1. Gambar kurva t vs Cp di kertas
semilog----- tentukan modelnya2. LR t vs ln Cp di fase eliminasi------------- pers: ln Cp = ln B- β.t (slope: –β)3.Berdasarkan pers LR cari Cp’ pada fase
distribusi4. Dihitung ΔCp atau Cr= Cp (dist)- Cp’ 5. Pers Ln Cr = ln A –αt (slope: –α)
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Waktu, jam
Kons. (Cp)
(μg/ml)
Cp’ Δ =(Cp-Cp’)
2 680,35 245,59 434,76
5 446,48 232,27 214,21
10 277,33 211,65 65,68
LR, t vs.lnCpR=0,999β=0,018lnB=5,54
B =254,68 μg/ml
lnCp = -0,018 t + 5,54
LR, tdist vs.
lnΔR=0,999α=0,24
lnA=6,55A =697,64
μg/ml
120 27,38
150 15,68
180 8,98
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mlmlg
g
Cp
DivVV
mlgAUC
BAAUC
mlgCp
BACp
sentral 07,105/32,952
000.100
/72,055.17
018,0
68,254
24,0
64,697
/32,95268,25464,697
01
0
0
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1
01.2
1
2
0
2
2.1
077,0
32,952
24,0.68,254018,0.64,697..
12,0
)24,0.68,254018,0.64,697(32,952)24,0018,0(68,254.64,697
)..(
)(.
menit
Cp
BAk
menit
BACp
BAk
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mlg
AUC
DivVdVd
mlVVssV
ml
Vk
kkVVVss
area
73,32572,17055.018,0
000.100
.
74,16307,10581,268
81,268077,0
077,012,0
.
12
11.2
1.22.121
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mlg
eeCp
g
CpVdAb
menitmlg
AUC
DivCL
tareamenit
T
/38,3
.68,254.64,697
97,110038,3.73,325
.
/86,572,17055
000.100
240.018,0240.24,0)240(
)()240(
1