DRUG DISTRIBUTION

 Patterns of drug distribution reflect

certain physiological factors and
physiochemical properties of drugs.
Phases of distribution:

• An initial phase of distribution may be

distinguished that reflects cardiac output
and regional blood flow.
 Heart, liver, kidney, brain and other
well-perfused organs receive most of the
drug during the first few minutes after
absorption.
(2) Delivery of drug to muscle, most
viscera, skin and fat is slower, and these
tissues may require several minutes to
several hours before steady state is attained.
(3) A third phase of distribution is also
possible for some drugs where the drug
slowly accumulates in some tissues like
fat tissue and other tissues.
 These tissues can become reservoirs for
the maintenance of the plasma
concentration.
Factors influencing drug distribution
1. Membrane permeability of various tissues
2. Blood flow
3. Plasma protein binding
4. Regional differences in pH
5. Capillary permeability
 Drug Reservoirs

 The body compartments in which a drug

accumulates are potential reservoirs for
the drug.
 If stored drug is in equilibrium
with that in plasma and is released as the
plasma concentration declines, a
concentration of the drug in plasma and at
its locus of action is sustained, and
pharmacological effects of the drug are
prolonged.
Fat as a reservoir:
 Many lipid-soluble drugs are stored fat.

In obese persons, the fat content of the

body may be as high as 50% and fat can
serve as an important reservoir for
lipid-soluble drugs.
 For example, as much as 70% of the
highly lipid-soluble barbiturate thiopental
may be present in body fat 3 hours after
administration.
Bone:
 Tetracycline antibiotics and heavy metals
may accumulate in bone and bone can
become a reservoir for the slow release of
toxic agents such as lead or radium into the
blood; their effects can thus persist long
after exposure has ceased.
In a suspected overdose, the most
appropriate site for sampling to identify
the drug depends on the drug’s chemical
characteristics:
 Acidic drugs will concentrate in the
plasma and blood is an appropriate
sample site for identifying the drug.
The stomach is a reasonable site for
sampling basic drugs.
 The actions of amphetamine can be
prolonged by ingesting bicarbonate to
alkalinize the urine.
 As a result of alkalinization, an
increasing fraction of urinary amphetamine
is in the un-ionized form and as such is
readily reabsorbed.
urine circulation

out
 Volume of distribution (Vd)

 The actual volume in which drug

molecules are distributed within a
patient’s body cannot be measured.
 However, an apparent volume of

distribution (Vd) can be obtained and may

be of some clinical usefulness.

 Vd is defined as the factor relating the
concentration of drug in blood to the total
amount of drug in the body:
Volume of Distribution (Vd) =

Amount of drug in the body

Plasma drug concentration
 The volume of distribution can serve as a
guide in determining whether a drug is
distributed primarily into plasma or into
extracellular space.
 In some clinical situations it is important
to achieve the target concentration
instantaneously.
 A loading dose is often used and Vd is the

determinant of the size of the loading dose:

Loading dose (mg) =

(Vd, L)x (Desired plasma concentration, mg/L)

 Many acids including salicylates,
sulfonamides and penicillins are either too
highly bound to plasma proteins or too
water soluble to enter cells and adipose
tissue in large amounts. Therefore, their
Vd is low (approximately 8-20 L).
 In contrast, bases are taken up by many
tissues. Concentrations in plasma are low,
and Vd exceeds the volume of total body

fluids.
For example, Vd for antihypertensive

drug propranolol is about 200L.