Lecture 6 — Volume of Distribution, Protein Binding and Repeated Dosing
Volume of distribution (Vd)
• Vd relates the amount of drug in the body to its measured plasma concentration. Formula: Vd = amount of drug in the body / plasma drug concentration.
• Vd is an apparent mathematical volume, not necessarily an anatomical compartment. A drug with Vd around 12 L may be distributed in extracellular fluid without entering cells.
• An apparent Vd may exceed total body water (approximately 40 L in the lecture’s 70-kg adult example) when plasma concentration is low because drug is extensively stored or bound in tissues.
• The lecture gives thiopental as an example of a highly lipid-soluble drug that may accumulate in fat and have a large Vd.
Distribution differs between drugs
• Different physicochemical characteristics lead to different volumes of distribution, even within the same person.
• A larger Vd generally indicates more extensive distribution outside plasma, not a literal increase in the body’s physical volume.
Plasma protein binding
• Many drugs bind to plasma proteins, including albumin and alpha1-acid glycoprotein (AGP).
• Only the unbound fraction is immediately available to bind receptors, undergo metabolism, and be eliminated.
• Phenytoin is approximately 90% protein bound in the lecture example. Changes in binding due to renal disease or drug interactions may meaningfully change its free fraction.
• For many other drugs, displacement from protein binding sites has less sustained clinical impact than a simple change in free fraction might suggest.
Single-dose versus multiple-dose kinetics
• Single doses are commonly used to characterize a drug’s concentration–time profile, with concentrations followed until they are no longer analytically detectable.
• In practice, medications are often given repeatedly before the previous dose has been completely eliminated. This causes accumulation until input and elimination balance at steady state.
What determines steady-state concentration?
• Higher doses or more frequent dosing can produce higher steady-state concentrations; elimination rate also affects the level reached.
• Time to steady state is governed by elimination half-life, not simply by increasing the dose or dosing frequency.
• The lecture uses an example of dosing every 8 hours for a drug with an 8-hour half-life: approximate steady state occurs after five half-lives, or around 40 hours.
Prepared for Dear Study. Review alongside the original university PDF for figures and slide-specific details.
