Low apparent volume of distribution (aVd) indicates:
Ans. A. Drug is not extensively distributed in organs and tissuesVolume of distribution (Vd ) is defined as ratio of the amount of drug in the body and the plasma concentration of drug (Cp)Vd = Total dose administered to patient/Cp Volume of distribution can be determined by various factors:A. More plasma protein binding restricts drug to plasma, hence there will be less distribution to extravascular space and tissues (least Vd ).B. Polar compounds have slightly more volume of distribution (Vd :0.2L/kg)C. More tissue binding capacity or more lipid solubility will make drug to cross most of the membranes, including blood-brain barrier making volume of distribution more.D. Sequestration of drugs in the particular tissue makes its volume of distribution even more than whole blood volume (e.g., Chloroquine has large volume of distribution as it gets sequestered in the liver)Water (0.6 L/kg)Lipid soluble molecules: e.g., EthanolExtracellular water (0.2L/kg)Water-soluble molecules: e.g., Gentamicin Polar compoundsBlood (0.08L/kg)Plasma (0.04L/kg)Strongly plasma protein-bound molecules and very large molecules: e.g., heparin
Drug is not extensively distributed in organs and tissues
Low bioavailability
Low T 1/2
Very low efficacy
General Pharmacology