Model Kompartemen

satu terbuka
 Pemberian IV
• Tubuh dianggap sebaga satu sistim tunggal (satu
ruang/satu kompartemen)
• Terbuka karena obat yang masuk akan
dimetabolisme dan akhirnya diekresi ke luar
tubuh
• Diasumsikan perubahan kadar obat dalam darah
mencerminkan perubahn obat dalam jaringan.
• Assumsi : eliminasi obat dari tubuh mengikuti
first order kinetik
Jika obat diberikan secara IV bolus
• Obat langsung mencapai
sirkulasi sitemik
• Diasumsikan obat terdistribusi
homogen kesemua ruang
kompartemen dalam waktu
singkat
• Kesetimbang antara darah dan
jaringan dalam waktu singkat
• Tubuh sebagai ruang satu
kompartemen dg vol tertentu
 Tetapan laju eliminasi
• Laju eliminasi mengikuti laju kinetika order
pertama
• Eliminasi melalui
• Metabolismen (km)
• Ekresi (ke)
• Tetapan laju eliminasi
 Obat IV bolus
• Perubahan obat di dalam tubuh

• Jika diintegralkan
• Persamaan 3.3 dapat juga di tulis
 Volume distribusi
• Vd : menyatakan suatu faktor yg diperhitungkan dlm memperkiran
jumlah obat dlm tubuh dari kons obat yg ditentukan

• Subsitusi 3.5 ke 3.3

• Dapt juga ditulis

 Contoh
• 1 gram obat dilarutkan air sejumlah air. Dari
penetapan kons diketahui 1 mg/ml. Vd brp
• Db = Vd .cp
• 1000 mg = Vd 1mg/ml
• Vd = 100 ml

• Vd = dosis/Cpo = Dbo/Cpo
• Grafik semi log Cpo dengan ekstrapolasi
• Iv bolus, pada saat t = 0
• Cpo = Dosis /Vd Dosis = Vd .Cpo
• Cpo dapat diperoleh ekstrapolasi garis regresi
ke sumbu Y.
• Vd jug bisa di hitung dari dosis, tetapan laju
eliminasi dan AUC dati t0 sampai t tak hingga
• dDb/dt = -k .Db dDb/dt = - k Vd. Cp
• dDb= -k Vd.Cp. Dt
• Karena k dan Vd konstan jika di integrasikan
•

•
 Cairan kompartemen tubuh
Cairan Persen bb Persen cairan
kompartemen tubuh
Plasma 4,5 7,5
Cairan ekstra 27 45
seluler
Cairan intra 33 55
total
Cairan tubuh 60 100
total
 PROBLEMS
• A 70-kg volunteer is given an intravenous dose of an
antibiotic, and serum drug concentrations were
determined at 2 hours and 5 hours after
administration. The drug concentrations were 1.2
and 0.3 micro g/mL, respectively. What is the
biologic half-life for this drug, assuming first-order
elimination kinetics, Vd = 0,5 L/kgbw? Cp to, Dosis IV
. MEC 0,15 micogram/ml how long action duration
• A 50-kg woman w as given a single IV dose of
an antibacterial drug at a dose level of 6
mg/kg. Blood samples were taken at various
time intervals. The concentration of the drug
(Cp) was determined in the plasma fraction of
each blood sample and the following data
were obtained
t (hour) C p ( microg/mL
0.00 ?
0.25 8.21
0.50 7.87
1.00 7.23
3.00 5.15
6.00 3.09
12.0 1.11
18.0 0.40
 Question
1. What are the values for Vd, k, and t 1/2 for this
drug?
2.  His antibacterial agent is not effective at a plasma
concentration of less than 2 micro g/mL. What is
the duration of activity for this drug?
3. How long would it take for 99.9% of this drug to be
eliminated?
4.  If the dose of the antibiotic were doubled exactly,
what would be the increase in duration of activity?
 Grafik pada kertas (biasa) milimeter
9

5
Kadar

0
0 2 4 6 8 10 12 14 16 18 20

waktu
 Grafik pd kertas semilog
10

0.1
0 2 4 6 8 10 12 14 16 18 20

Waktu
 Grafik ln Cp
2.50

2.00 f(x) = − 0.170282105970003 x + 2.14869756133961

R² = 0.999999444180398

1.50

1.00
ln Cp

0.50

0.00
0 2 4 6 8 10 12 14 16 18 20

-0.50

-1.00

-1.50

Waktu
• A new drug w as given in a single intravenous
dose of 200 mg to an 80-kg adult male patient.
After 6 hours, the plasma drug concentration
of drug w as 1.5 mg/100 mL of plasma.
Assuming that the apparent Vd is 10% of body
weight, compute the total amount of drug in
the body fluids after 6 hours. What is the half-
life of this drug?
• A new antibiotic drug w as given in a single
intravenous bolus of 4 mg/kg to five healthy
male adults ranging in age from 23 to 38 years
(average weight 75 kg). The pharmacokinetics
of the plasma drug concentration–time curve
for this drug fits a one- compartment model.
The equation of the curve that best fits the data
is
Determine the follow ing (assume units of micro g/mL for C
p and hr for t):

1. What is the t 1/2?

2. What is the Vd?
3. What is the plasma level of the drug after 4 hours?
4. How much drug is left in the body after 4 hours?
5. Predict what body water compartment this drug might
occupy and explain why you made this prediction.
6. Assuming the drug is no longer effective w hen levels
decline to less than 2 microg/mL, when should you
administer the next dose?