10 Questions
What is the primary reason for warfarin having a small volume of distribution?
High plasma protein binding
How does the volume of distribution of a drug like digoxin relate to its binding to tissues?
High tissue binding contributes to a large volume of distribution
In the equation V= CL/ke, what does 'CL' represent?
Elimination rate constant
How do plasma protein binding drug interactions affect the volume of distribution?
Increase the free fraction in serum, increasing volume of distribution
What parameter does half-life describe in pharmacokinetics?
Rate of elimination
What is the purpose of the volume of distribution (V) parameter in pharmacokinetics?
To determine the required loading dose (LD) to achieve a particular steady-state drug concentration
How does the volume of distribution (V) relate the amount of drug in the body (X) to the serum drug concentration (C)?
C = X / V
How does the volume of distribution (V) differ between a drug that is primarily contained in the blood (e.g., warfarin) and a drug that distributes widely in the body and is mostly bound to tissues (e.g., digoxin)?
Drugs contained primarily in the blood have a smaller V, while drugs distributed widely in the body have a larger V
How does the size (volume) of a person's body affect the volume of distribution (V) for a drug?
A larger person will have a larger V than a smaller person
What is an important determinant of the volume of distribution (V) for a drug?
All of the above
Study Notes
Volume of Distribution
- Warfarin has a small volume of distribution due to high binding to serum albumin, resulting in a small free fraction of drug in the blood (fB).
- Digoxin has a large volume of distribution because it is highly bound to tissues (primarily muscle), resulting in a small free fraction of drug in the tissues (fT).
Factors Affecting Volume of Distribution
- The volume of distribution (V) is determined by the actual volume of blood (VB) and the size of various tissues and organs of the body (VT).
- Body size affects volume of distribution; a larger person would have a larger volume of distribution for a drug.
- The binding of a drug in the blood or serum compared to its binding in tissues is an important determinant of the volume of distribution.
Drug Interactions and Volume of Distribution
- When a drug that is highly bound to plasma proteins is given concurrently with a second drug that is also highly bound to the same plasma protein, the second drug competes for plasma protein binding sites, displacing the first drug and increasing its free fraction in the serum (fB).
- This leads to an increased volume of distribution.
Elimination and Half-Life
- Serum concentrations of a drug decline in a curvilinear fashion, but decrease in a linear fashion on a semilogarithmic axis during the elimination phase.
- The time it takes for serum concentrations to decrease by half in the elimination phase is the half-life (t1/2), which is a constant and has the dimension of time.
Loading Dose and Steady State Concentration
- The loading dose (LD) required to achieve a particular steady-state drug concentration is determined by the volume of distribution (V): LD = Css V.
Learn about the concept of volume of distribution, an important pharmacokinetic parameter that determines the loading dose needed to achieve a specific drug concentration. Understand how this parameter relates drug serum concentrations to the amount of drug in the body.
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