dela Chica, Mary Anne Gabrielle M.

IP 161 Lec – Seatwork 3

1. The values of the volume of distribution of three drugs (A, B and C) are given below. For each drug,
discuss the information provided by the value of this parameter. Address specifically the potential
volume into which the drugs distribute, the relative distribution of the drugs between plasma and
tissue and the binding to the tissues and plasma protein.

Drug A: 0.5 L/kg or 35 L in a 70 kg person

Drug B: 0.143 L/kg or 10 L in a 70 kg person
Drug C: 14.3 L/kg or 1000 L in a 70 kg person

Based on the volume of distribution, drugs A and B are potentially distributed into the extracellular fluid
(Vd = 15 L/kg), while Drug C is distributed into the total body water (Vd = 40 L/kg). In terms of relative
distribution, Drug B has the lowest volume of distribution, which indicates that it is least distributed into
the tissues and is more concentrated in the plasma. This is followed by Drug A, while Drug C is the most
distributed among the three. In terms of protein binding, Drug B has the strongest binding to plasma
proteins and the weakest binding to tissue proteins. This is followed by Drug A, while Drug C has the
weakest binding to plasma proteins and the strongest binding to tissue proteins.

2. Theophylline has a volume of distribution of 0.50 L/kg

a. A 40 kg child has a theophylline plasma concentration of 10 mg/L. How much drug is in
the child's body?
Dose = Vd * Cp0 = 0.50 L/kg * 40 kg * 10 mg/L = 200 mg
b. A therapeutic plasma concentration of 12 mg/L theophylline is desired in a 110 kg male
patient. How much drug will be in his body at this plasma concentration?
Dose = Vd * Cp0 = 0.50 L/kg * 110 kg * 12 mg/L = 660 mg

3. A drug binds extensively to albumin. When it is administered with valproic acid, it is displaced from its
protein binding site and the fraction bound in the plasma (fu) increases. How will this affect the volume
of distribution?

Increasing the fraction unbound in the plasma will lead to a higher plasma concentration. Since the drug
is more concentrated in the plasma given the same dose, the volume of distribution is decreased.

4. Amiodarone has a volume of distribution of 4600 L. If the plasma concentration is 1 mg/L:

a. How much drug is in the body?
Dose = Vd * Cp = 4600 L * 1 mg/L = 4600 mg
b. How much drug is in the plasma?
1 mg/L * 3 L = 3 mg
c. How much drug is in the tissue?
4600 mg – 3 mg = 4597 mg
d. What percentage of the drug in the body is in the tissues?
(4597 mg/4600 mg) * 100 = 99.93%

5. Warfarin has a volume of distribution of 8 L. If the plasma concentration is 1 mg/L:

a. How much drug is in the body?
Dose = Vd * Cp = 8 L * 1 mg/L = 8 mg
b. How much drug is in the plasma?
 1 mg/L * 3 L = 3 mg
c. How much drug is in the tissue?
8 mg – 3 mg = 5 mg
d. What percentage of the drug in the body is in the tissues?
(5 mg/8 mg) * 100 = 62.5%

6. R.S. is a pregnant woman who has been stabilized on phenytoin for 15 years. She is in her third
trimester and her plasma concentration is found to be 7.0 mg/L. The therapeutic range for phenytoin
is 10 to 20 mg/L when the plasma protein binding is normal (fu=0.1). R.S.'s albumin level is measured
and found out to be low, and her fu value for phenytoin is estimated to be 0.15. Is the measured
phenytoin concentration therapeutic, toxic, or subtherapeutic?

fu = conc. unbound/total conc.

0.1 = x/(10 mg/L)
x = 1.0 mg/L

0.1 = x/(20 mg/L)

x = 2.0 mg/L

0.15 = x/(7 mg/L)

x = 1.05 mg/L

The measured phenytoin concentration is therapeutic since the unbound concentration (1.05 mg/L) is
within the unbound therapeutic range (1.0 to 2.0 mg/L).