2. Clinical pharmacokinetics: application of the parameters "volume of distribution" and "plasma protein binding" of drugs in clinical practice.
Explains how the volume of distribution and plasma protein binding of drugs are used in clinical practice. Covers the apparent nature of Vd, a three-band table grouping drugs by Vd with examples, and how Vd guides loading doses and dialysis decisions. Then describes which drugs bind albumin or α1-acid glycoprotein, why only the free fraction is active, and a table of clinical situations such as hypoalbuminaemia, uraemia and displacement interactions.
Topic 2 of 30 in the MU Sofia syllabus for Clinical Pharmacology (Medicine, Year 5). The free AceMed note covers it in 3 sections, about 286 words (3 min of reading), with 16 flashcards.
In this note
Introduction
Volume of distribution (Vd)
Plasma protein binding
Introduction
Pharmacokinetics (PK) describes what the body does to a drug: absorption, distribution, metabolism, elimination (ADME). It links the dose to the concentration; pharmacodynamics links the concentration to the effect. Two parameters describe distribution: the volume of distribution and plasma protein binding.
Volume of distribution (Vd)
Vd is the apparent volume the drug would occupy if it were everywhere at the same concentration as in plasma. It is not a real anatomical space:
Clinical use of Vd
Loading dose: the dose needed to reach a target concentration at once depends on Vd, not on clearance:
The loading dose is the same in kidney or liver failure (Vd is little changed), whereas maintenance doses are reduced.
Vd changes with body composition: lipophilic drugs have a larger Vd in obesity and the elderly; water-soluble drugs (e.g. aminoglycosides) have a larger Vd in oedema, ascites and sepsis, so dose by the right weight.
A drug with a very large Vd is not removed effectively by haemodialysis in overdose (e.g. digoxin, tricyclics); a small Vd drug can be (e.g. lithium, salicylate).
A large Vd lengthens the half-life (t½ = 0.693 × Vd / CL).
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