DISTRIBUTION

Dept. Pharmacology & Therapeutic

FK - USU
 Dose
Pharmacokinetic
ABSORBTION

DISTRIBUTION
Drug Concentration in Drug in tissue
sistemic circulation
ELIMINATION

Metabolism or Excretion
Drug concentration in site
drug action

Pharmacologic
effect
Response
Pharmacodynamic

Toxicity Efficacy
 Drug distribution is achieved primarily
through the circulatory system; a minor
component is contributed by the lymphatic
system.

The concentration of drug in plasma is

often used to determine therapeutic drug
levels, because the amount of drug that is
actually taken up by the target organ is
difficult to measure.
 The Volume of Distribution of a drug (Vd)
represents the fluid volume that would be
required to contain the total amount of
absorbed drug in the body at a uniform
concentration equivalent to that in the
plasma at a steady state.

The capacity of bloodstream and the various

body organs and tissues to take up and
retain a drug depends on both the volume
(mass) of the tissue and the density of
specific and non specific binding sites for the
drug within that tissue.
 Plasma Protein Binding
Plasma protein binding tends to reduce
the availability of a drug for diffusion or
transport into the drugs target organ
because, in general, only the free or
unbound form of the drug is capable of
diffusion across membranes.
 Plasma protein binding may also reduce
the transport of drugs into such non
vascular compartments as adipose tissue
and muscle

Theoretically, plasma protein binding could

be important as a mechanism for some
drug drug interactions.
 MODELING THE KINETICS AND
THERMODYNAMICS OF DRUG DISTRIBUTION

Most drugs are distributed rapidly from the

systemic circulation (intravascular
compartment) to other compartments in the
body.

This distribution phase results in a sharp

decrease in the plasma drug concentration
shortly after intravenous administration of a
drug bolus.
 Even after the drug equilibrates among its
tissue reservoirs, the plasma drug
concentration continues to decline because
of drug elimination from the body.

The rate of decline of plasma drug

concentration during the elimination phase is
slower than that during the distribution
phase, because drug in the tissue reservoir
is in equilibrium with that in the intravascular
compartment, and therefore, drug can diffuse
from the tissue back into the blood
The tendency for a drug to be taken up by
adipose and muscle tissue during the
distribution phase result in a set of the
dynamic equilibria among drug
concentrations in the various body
compartments.
 The rapid decline of plasma drug
concentration after administration of an
intravenous bolus of drug can be
approximated more accuratelyby using a
four compartement model consisting of
blood and vessel-rich, muscle-rich, and
adipose-rich tissues.

Drugs tend to exit from the vessel-rich group

first, followed by the muscle group and then
the fat group.
 Delivered of drug depend on:
- Blood flow
- Hydrophobicity of drug
- Capillary permeability
- Affinity to plasma protein or tissue