Clinical Pharmacokinetics: Clearance, Volume of Distribution & Two-Compartment Models (Clinical Treatise 2011)
Predicting plasma drug concentrations requires rigorous integration of apparent volume of distribution, physiological clearance organs, and multi-exponential elimination.
Pharmacological Mechanism & Kinetic Schema
Apparent Volume of Distribution (Vd) and Tissue Binding
Vd does not represent a physical anatomical space, but the theoretical fluid volume required to account for all drug in the body at the same concentration as circulating plasma. Drugs with high tissue affinity and lipophilicity (e.g., Digoxin, Chloroquine) exhibit astronomical Vd values (> 500 L), whereas highly albumin-bound molecules (e.g., Warfarin) are restricted to the vascular space (Vd ~ 7 L).
Organ Clearance and the Extraction Ratio (E)
Clearance is the volume of biological fluid completely cleared of drug per unit time. For high-extraction-ratio drugs (E > 0.7, such as Propranolol and Lidocaine), hepatic clearance is blood-flow-limited, rendering them exquisitely sensitive to hemodynamic changes. Low-extraction drugs (E < 0.3) are capacity-limited by intrinsic enzyme activity.
Multi-Compartmental Distribution Kinetics
Following rapid intravenous bolus injection, many drugs distribute rapidly into highly perfused central organs (heart, lungs, liver, brain) before slowly equilibrating into peripheral muscular and adipose compartments, generating distinct bi-exponential plasma decay curves governed by alpha and beta hybrid rate constants.
Clinical Pharmacologist & Biochemist · Specialist in Pharmacokinetics & Hospital Pharmacotherapy · Published on April 20, 2011 at 02:05
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