Volume of distribution of Paracetamol – Pharmacology MCQ

Volume of distribution of Paracetamol is?
A. 500 ml/kg body weight
B. 1 L/kg body weight
C. 5 L/kg body weight
D. 25 L/kg body weight

Correct answer : B. 1 L/kg body weight

Volume of distribution

• After a drug enters the blood, it is distributed to various other tissues.
• The pattern of drug distribution is influenced by:
  • Lipid solubility (lipid insoluble drugs are limited to the extracellular compartment)
  • Degree of plasma protein / tissue protein binding
  • Existence of tissue specific transporters
  • Ionisation of the drug at physiological pH (depends on pKa)
  • Variation in the blood flow to different tissues.

Apparent volume of distribution

• Assuming that the body is a homogeneous compartment with a volume of V, the apparent volume of distribution can be calculated as follows:
  • V = Amount of drug administered IV / Plasma concentration of the drug
• But the body is not a homogenous compartment.
• Some drugs may be concentrated in certain body tissues.
• In that case, even after administering a large quantity of the drug, the plasma concentration will be low.
• Here, the apparent volume of distribution is large.
• Other drugs may be limited to the intravascular compartment.
• Here, the volume of distribution is equal to the blood volume.

Volume of distribution of some important drugs:

• Drugs with high plasma protein binding like warfarin and diclofenac are mostly limited to the intravascular compartment. Here the volume of distribution is very low. ( approximately 0.15 L/kg)
• Lipid insoluble drugs like streptomycin and gentamicin do not enter the intracellular compartment. Hence their volume of distribution is equal to the extracellular fluid volume. ( approximately 0.25 L/kg)
• Drugs which are sequestered in body tissues have a high volume of distribution. e.g. Morphine (3.5 L/kg), Propranolol (4 L/kg), Digoxin (6 L/kg).

Clinical significance:

• Drugs with high volume of distribution are difficult to remove via hemodialysis in cases of poisoning.
• Volume of distribution may be altered in disease conditions by various mechanisms like change in membrane permeability, variation in the distribution of body water and alteration in the drug binding proteins.

Ref: Essentials of Medical Pharmacology, K D Tripathi, 7th ed, page 2, 17, 18