PCL201H1 Lecture Notes - Lecture 9: Body Composition, Lipophilicity, Extracellular Fluid

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14 Sep 2016
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PCL201
Winter 2014
Lecture 9 Drug Distribution
1. Introduce drug distribution in body compartments
2. Define the term Volume of Distribution (Vd)
3. Examine how Vd is calculated
4. Examine the importance of Vd
5. Overview drug-related factors affecting Vd
1. Introduce drug distribution in body compartments
Following administration and absorption, the drug distributes from the systemic circulation to
intracellular and interstitial fluid
Distribution depends on:
o Physiochemical properties of the
drug
o Plasma protein and tissue binding
o Blood flow and capillary permeability
o Patient-related factors
TBW varies with:
o Body composition (obese vs. lean)
o Age (children vs. elderly)
o Gender
Small molecules (e.g. ethanol) with no
protein binding or tissue accumulation
equilibrate with TBW
Drugs must permeate cell membranes to
reach the ICF (to act on intracellular targets)
Drugs distribute through the ECF faster than permeating membranes (to act on surface
receptors)
Plasma: liquid portion of the blood
o Serum is plasma without clotting factors
o Drug concentration often measured in plasma or serum dependent on hematocrit
Hematocrit: % of RBC
Drugs (especially acidic ones) may reversibly bind to proteins like α1-glycoprotein and albumin
cannot permeate barriers and remain in the blood
Drugs that localize are unequally distributed and remain longer in the body
2. Define the term Volume of Distribution (Vd)
Vd (actual): anatomical volume available to drug
Vd (apparent): hypothetical volume of plasma into which the drug appears to distribute
Calculations assume Vd (apparent) and equal distribution
Vd = dose/concentration
o Volume of distribution is proportional to dose and inversely proportional to
concentration
3. Examine how Vd is calculated
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