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D 0 C av kVD
SF
D 0 C av CL T
CL T kVD , then
SF
Example
An adult asthmatic patient (age 55,78 kg)
has been maintained on an iv infusion of
aminophylline at a rate of 34 mg/hr.The
steady-state theophylline drug
concentration was 12 g/mL and total
body clearance was calculated as 3.0 L/hr.
Calculate an appropriate oral dosage
regimen of theophylline for this patient.
Solution
S = 0.85 (cause aminophylline, a soluble salt which contains 85%
theophylline)
F = 1 (theophylline is 100% bioavailable)
Do/ or the dose rate =34 mg/hr. To convert to oral theophylline, S
& F should be considered :
SFD 0 0.851 34
Theophylline dose rate 28.9mg/hr
1
Solution (contd)
To convert the theophylline oral dose rate (28.9 mg/hr) to
a reasonable schedule for the patient with a
consideration of the various commercially theophylline
drug products:
the total daily dose = 28.9 mg/hr x 24 hr = 693.6 mg/day
possible theophylline dosage schedule:
700 mg/day or 350 mg every 12 hrs or 175 mg every 6
hrs.
The dose of 350 mg every 12 hrs could be given in
sustained-release form to avoid fluctuations.
Method 2
Assumes that the rate of iv infusion (mg/hr) is
the same desired rate of oral dosage
Using the example in method 1, the solution:
iv infusion rate = 34 mg/hr
the total daily dose of aminophylline = 34 mg/hr
x 24 hr = 816 mg, which equivalent to 816 x 0.85
= 693.6 mg of theophylline.
Thus 700mg of theophylline per day or 350 mg
controlled-release theophylline every 12 hours
Determination of dose
The drug dose is estimated to deliver a
desirable (target) therapeutic level of drug
to the body. The dose of a drug is
estimated with the objective of delivering a
desirable therapeutic level of the drug to
the body.
For many drugs, the desirable therapeutic
levels and pharmacokinetic parameters
are available in the clinical literature.
For a drug given in multiple doses for an
extended period of time, the dosage regimen is
usually calculated, so that the average Css (C av)
is within the therapeutic range.
The dose can be calculated with eq.:
1.44D 0 t 1 F
C av 2
VD
Where Do = dose, = dosing interval
Equations for Cssmax and Cssmin
D0 1
C max k
VD 1 e
D0 1 k
C min k e
VD 1 e
Effect of changing dose and dosing interval on
Cssmax and Cssmin and Cssav
C 1
max
k
C min e
Practice problem
The t elimination of an antibiotic is 3 hrs
with VDapp equivalent to 20% of BW. The
usual therapeutic range is between 5 and
15 g/mL. Adverse toxicity for this drug is
often observed at serum conc greater than
20 g/mL. Calculate a dosage regimen
(multiple iv doses) that will maintain the
therapeutic range.
Solution
C max 1 15 1
k ( 0.693 / 3)
C min e 5 e
e 0.231 0.333
-0.2314.76 = ,1.10- = hr
D 0 /VD
The dose was determine by eq:
maxC
Let VD= 20%BW = 200mL/kg 1 e k
Then Do = 2 mg/kg
So, the dose should be D 0 /200
2 mg/kgBW every 4.76 hrs 15 (0.231)(4.76)
The should be made as convenient as
1 e
Possible, let take 6 hrs, then we
Should calculate the Do again
Using nomograms and tabulation in
designing dosage regimens
Exp: Maintenance dose of theophylline when the Cp is not measured