Nama : Kelvin Fernando Pratama

NPM : 260110170107
FARMAKOKINETIK
Latihan Soal INTRAVENA MULTIPLE DOSAGE REGIMEN (MDR)

1. Gentamicin has an average elimination half-life of approximately 2 hours and an apparent

volume of distribution of 20% of body weight. It is necessary to give gentamicin, 1 mg/kg
every 8 hours by multiple IV injections, to a 50-kg woman with normal renal function.
Calculate!
(a) Cmax (ss)
(b) Cmin (ss)
(c) Cav (ss)
Answer
 Distribution Volume (Vd)
Vd=20 % × 50 kg=10 L=10,000 mL
 Elimination constant (k)
ln 2 ln 2
k= = =0.347 h−1
t 1 /2 2
 Drug fraction (f)
f =e−kτ =e−(0.347)(8) =0.0625
(a) Cmax (ss)
Cp0 D 0 1 (1 mg/kg)(50 kg) 1
C max ( ss )= = × = × =5.33 μg/ml
1−f Vd 1−f 10,000 mL 1−0.0625
the maximum plasma concentration is 5.33 μg/ml
(b) Cmin (ss)
Cp 0 × f D 0 f (1 mg/ kg)(50 kg) 0.0625
C min ( ss )= = × = × =0.33 μg /ml
1−f Vd 1−f 10,000 mL 1−0.0625
the minimum plasma concentration is 0.33 μg/ml
(c) Cav (ss)
FD 0 100 % ×50 mg
C av ( ss )= = =1.80 μg/ml
k . Vd . τ 0.347 h−1 ×10,000 mL × 8 h
the average plasma concentration is 1.80 μg/ml
2. A physician wants to give theophylline to a young male asthmatic patient (age 29 years, 80
kg). According to the literature, the elimination half-life for theophylline is 5 hours and the
apparent VD is equal to 50% of the body weight. The plasma level of theophylline required
to provide adequate airway ventilation is approximately 10 μg/mL.
(a) The physician wants the patient to take medication every 6 hours around the clock. What
dose of theophylline would you recommend (assume theophylline is 100% bioavailable)?
(b) If you were to find that theophylline is available to you only in 225-mg capsules, what
dosage regimen would you recommend?
Answer
 Distribution volume (Vd)
Vd=50 % × 80 kg=40 L=40,000 mL
 Elimination constant (k)
ln 2 ln 2
k= = =0.137 h−1
t 1 /2 5 h
(a) Recommended dose (D0)
D 0=C av ( ss ) . k . Vd . τ=10 μg /mL × 0.137 h−1 × 40,000 mL ×6 h=328.8 mg
the theophylline dosage that can be recommended is 328.8 mg (theophylline is 100%
bioavailable¿
(b) Dosage regimen
D0 225 mg
τ= = =4.11 h
C av ( ss ) × k ×Vd 10 μg/mL × 0.137 h−1 × 40,000mL
the drug is given every 4.11 hours if there are only 225 mg capsules

3. A drug has an elimination half-life of 2 hours and a volume of distribution of 40 L. The drug
is given at a dose of 200 mg every 4 hours by multiple IV bolus injections. Predict the
plasma drug concentration at 1 hour after the third dose!
Answer
 Elimination constant (k)
ln 2 ln 2
k= = =0.347 h−1
t 1 /2 2 h
 Plasma drug consentration 1 hour after the third dose (Cp)
 D 0 1−e−nkτ 200 mg 1−e−( 3) (0.347 )( 4 )
Cp= (
Vd 1−e −kτ
× e
−kt
= )
40,000 mL 1−e (
− ( 0.347 ) ( 4 ) )
× e− 0,347 1
( )( )

Cp=4.64 mg/ L
Plasma drug concentration is 4.64 mg/L

4. The elimination half-life of an antibiotic is 3 hours and the apparent volume of distribution is
20% of the body weight. The therapeutic window for this drug is from 2 to 10 μg/mL.
Adverse toxicity is often observed at drug concentrations above 15 μg/mL. The drug will be
given by multiple IV bolus injections.
a. Calculate the dose for an adult male patient (68 years old, 82 kg) with normal renal
function to be given every 8 hours!
b. Calculate the anticipated Cmax(ss) and Cmin(ss) values!
c. Calculate the Cav(ss) value!
d. Comment on the adequacy of your dosage regimen!
Answer
 Distribution volume (Vd)
Vd=20 % × 82 kg=16.4 L=16,400 mL
 Elimination constant (k)
ln 2 ln 2
k= = =0.231 h−1
t 1 /2 3 h
 Drug fraction (f)
−kτ −(0.231)(8)
f =e =e =0.157
(a) Dose of administration (D0)
D0=C max ( ss ) . Vd ( 1−f )=10 μg/mL× 16,400 mL(1−0.157)=138.252 mg
Dose to be given is 138.252 mg
(b) Anticipated Cmax(ss) and Cmin(ss) values
C max ( ss )=10 μg/mL
C min ( ss )=C max ( ss ) × f =10 μg /mL × 0.157=1.57 μg /mL
Anticipated Cmax (ss) and Cmin (ss) values are 10 μg/mLand 1.57 μg/mL
(c) Cav(ss) value
 FD 0 100 % ×138.252 mg
C av ( ss )= = =4.56 μg/ml
k . Vd . τ 0.231 h−1 ×16,400 mL ×8 h
Cav(ss) value is 4.56 μg /ml
(d) Dosage regimen adequacy
C min ( ss )=1.57 μg /mL
1.57 mg/mL < 2 mg/mL (minimum plasma consentration of this antibiotic) so that it
takes a change at a time period of 6 hours (according to the frequency of conventional
administration or 4 times a day). Thus, the dosage that needs to be administered is:
D0=C max ( ss ) . Vd ( 1−e−kτ ) =10 μg /mL ×16,400 mL ( 1−e−(0.231) (6 )) =122.98 mg
D0 ≅ 123 mg

C min ( ss )=C max ( ss ) × e−kτ=10 μg /mL ×e−(0.231)(6 )=2.5 μg/mL

Administering 123 mg every 6 hours is able to provide a therapeutic window between 2.5
μg/mL and a maximum of 10 μg/mL