PHARMACOKINETIC PARAMETERS

VOLUME OF DISTRIBUTION

Distribution
Distribution is the dispersion of the drug among the various organs or compartments within the body. The apparent volume of distribution (Vd), has been devised to describe the distribution of the drug. Vd is the volume into which the drug appears to distribute and it is calculated from the dosage and the concentration of drug in the blood. Vd = D/(Cp x k)

Vd
Apparent volume of distribution is the theoretical volume that would have to be available for drug to disperse in if the concentration everywhere in the body were the same as that in the plasma or serum, the place where drug concentration sampling generally occurs. V(t) is an imaginary volume correlating the amount of a drug present in the body to the concentrations of the drug measured in the reference body fluid, usually plasma, at any given time t. V(t) can vary depending on the reference fluids in which the drug concentrations are measured. In general, the volume of distribution is referred to the plasma drug concentrations, unless otherwise indicated. As an independent parameter, V(t) is indicative of the extent of space or volume into which the drug is distributed, referred to drug concentration, not the rate of distribution. How fast the distribution occurs can be estimated by distributional clearance (Cld).

Important Concepts
VD is a theoretical Volume and determines the loading dose. Clearance is a constant and determines the maintenance dose. CL = kVD. CL and VD are independent variables. k is a dependent variable.

Volume of Distribution
An abstract concept Gives information on HOW the drug is distributed in the body Used to calculate a loading dose

Volume of Distribution
Example: Assume that 100 g of alcohol are ingested by a man who weighs 70 kg and the blood level is found to equal 2.38 g/L. Vd = D/(Cp x k) Vd = 0.100 kg/(0.00238 kg/L x 70 kg) Vd = 0.60 L/kg or 42 L for this man

Volume of Distribution, Clearance and Elimination Rate Constant

V

Volume 100 L
Clearance 10 L/hr

Volume of Distribution, Clearance and Elimination Rate Constant

V

V2 Cardiac and Skeletal Muscle

Volume 100 L (Vi)

Clearance 10 L/hr

V2 Cardiac and Skeletal Muscle V

Volume 100 L (Vi)

Clearance 10 L/hr

Volume of Distribution = Dose_______ Plasma Concentration

V2 Cardiac and Skeletal Muscle V

Volume 100 L (Vi)

Clearance 10 L/hr

Clearance = Volume of blood cleared of drug per unit time

V2 Cardiac and Skeletal Muscle V

Volume 100 L (Vi)

Clearance 10 L/hr

Clearance = 10 L/hr Volume of Distribution = 100 L What is the Elimination Rate Constant (k) ?

CL = kV k = 10 Lhr -1 = 0.1 hr -1 100 L

10 % of the Volume is cleared (of drug) per hour k = Fraction of drug in the body removed per hour

CL = kV
If V increases then k must decrease as CL is constant

Volume of Distribution
Vd values range from about 5% of body volume to as high as 400 L. The latter figure is much higher than anyones total volume, so Vd is an artificial concept. Its importance lies in the fact that it will predict whether the drug will reside in the blood or in the tissue. Water soluble drugs will reside in the blood, and fat soluble drugs will reside in cell membranes, adipose tissue and other fat-rich areas.

Volume of Distribution
Volume of Distribution also relates to whether a drug is protein bound, Drugs that are charged tend to bind to serum proteins. Protein bound drugs form macromolecular complexes that cannot cross biological membranes and remain confined to the bloodstream. Pathological states may also change Vd. Because Vd mathematically relates blood concentration to dosage it may be employed in interpretation of laboratory results. Because Vd may be useful for providing an estimate of dosage, it follows that it can help estimate the amount of antidote to be given. Vd is able to indicate whether there is any value in trying to enhance elimination as, for example, by dialysis.

Volume of Distribution

 Volume of distribution is possibly the most important pharmacokinetic parameter. It indicates whether a drug is to be found primarily in the blood or in another bodily site. Free and Bound Drugs Volume of distribution depends, among other factors, on the extent of the protein binding of a drug. Because only the free form is active but the laboratory result expresses the total drug concentration, the result is misleading if a patient has an abnormal free fraction. Volume of distribution is affected by many factors:
It may be higher in overdose It suggests that drug testing is worthwhile if the Vd is low It enables calculation of a dose from a blood level or vice versa