Computation of Drug

Parameter

DRUG PARAMETERS:
1.Therapeutic Index -is a ratio of a lethal dose 50 [LD ] to the effective dose 50 [ED ]
50 50
  TI= LD 50

      ED 50

    If a particular drug has an LD of 1000 mg and an ED of 100 mg, the      

50 50

therapeutic index would be 10 mg.

TI= 1000 mg
100 mg

TI= 10 mg

2. Bioavailability
On Absorption:
 Problem: If 10 ml of an elixir containing 4mg/ mL of a drug is bioequivalent to a 30 mg
tablet having a bioavailability factor of 1.2, what is the bioavailability factor [f] of the
elixir?

Tablet
 Dose = 30 mg
 Bioavailability factor = 1.2

Elixir
 Volume= 10 mL
 Concentration = 4 mg/mL
 Bioavailability factor = ???

Step 1 - Determine drug dose from elixir

10 mL × 4 mg = 40 mg
1mL
Step 2 - Determine bioavailability factor (f) for elixir

Ftab × Dosetab = Felixir × Doseelixir

1.2 × 30 mg = x × 40 mg

0.9 = x

3. [About Bound and Unbound Drugs]

 Problem 1: If an equilibrium one-fourth of the amount of drug substance is bound to
protein, what would be the alpha value of the drug?
Definitions and equation:

What is Alpha Value=C u

C    t

C Bound drug concentration

b=

C Unbound drug concentration

u=

C Total drug plasma concentration

T=

Step 1 – one-fourth of a drug substance in the blood is bound to protein (C B)

CT = C B + C U 1 (CT) = 1 (CB) + 3 (CU)

4 4

Step 2 – what would be the alpha (a) value of the drug?

Alpha (a) = Cu
CT

3 (Cu)
Alpha (a) = 4 = 3 = 0.75
1 (CT) 4

Problem 2 If a tablet administered was 500 mg and presuming from this dose one-third
:

in the blood was bound to protein what is the alpha value of the drug?
,

Step 1 – one-third of a drug substance in the blood is bound to protein (C B)

CT = CB + C u 1 (CT) = 1 (CB) + 2 (CU)

3 3

Step 2 – What would be the alpha (a) value of the drug?

Alpha Value = CU
CT
Alpha (a) = 2 =2 = 0.67
3 3
1
500 mg × 0.67 = 355 mg unbound

4. About volume of distribution

Sample problem: The volume of distribution for a drug has been determined to be 68 L.
Calculate the expected drug plasma concentration of the drug in microgram per milliliter
[ml] immediately after intravenous dose of 10 mg.

Vd = D               
        Cp

Where Vd= Volume of distribution

D=Dose
Cp=plasma drug concentration

Dose (D) = 10 mg
Volume of Distribution (Vd) = 68 L
Plasma Concentration (Cp) = ??? mcg/mL

Step 1 – Convert dose from milligram (mg) to microgram (mcg)

10 mg × 1000 mcg = 10000 mcg

1 mg

Step 2 – Convert volume of distribution (Vd) from liters (L) to milliliter (mL)

68 L = 1000 mL = 68,000 mL
1L

Step 3 – Solve for plasma concentration ( C p) using volume of distribution (Vd) formula

Vd = D thus Vd × Cp = D thus Cp= D = 10000 mcg = 0.147 mcg/mL

Cp Vd 68,000 mL

5. Half-Life
In brief:
Half-life (t½) is the time required to reduce the concentration of a drug by half.
 1. The formula for half-life is (t½ = 0.693 × Vd /CL)
2. Volume of distribution (Vd) and clearance (CL) are required to calculate this
variable.
 
Refer to Uploaded Video in GCR

Sample problem 1:
The half -life of Fe-59 is 4.8 minutes. If you start with 200 grams of Fe, how many
grams would be left after 14.4 minutes have passed?

1/2 Time (minute) Amount (grams)

0 0 200 grams

1 4.8 minutes 100 grams

2 9.6 minutes 50 grams

3 14.4 minutes 25 grams

Answer: 25 grams would be left after 14.4 minutes have passed

Sample problem 2:
The half-life of Pd-100 is 8 days. After 24 days a sample have been reduced to a mass
of 8 grams. What is the starting mass?

1/2 Time (days) Amount (grams)

0 0 64 grams
1 8 days 32 grams
2 16 days 16 grams
3 24 days 8 grams

Answer: 64 grams is the starting mass