Volume Distribution

CONCEPT OF VOLUME OF DISTRIBUTION OF DRUGS:

DEFINITION OF VD
Add DRUG
to Beaker

Obtain Sample

Assay for [Drug]

(Stir)
Calculate Volume
[Drug] = Amount Added Volume of Beaker
Volume of Beaker = Amount Added [Drug]

Distribution. Where do drugs go?

CONCEPT OF VOLUME OF DISTRIBUTION OF DRUGS:

DEFINITION OF VD
Dose Body
with DRUG

Obtain Plasma Sample

Assay for [D]P

Calculate Volume
(This volume is called VD)

By DEFINITION: VD = A/[D]P
(where A is amount of drug in body and [D]P is concentration of drug in plasma)

Volume of distribution
Relative size of various
distribution volumes
within a 70-kg
individual

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Interstitial
fluid
represents
about
15% of the
total body weight.
Intracellular
fluid
(fluid inside cells) 40% of
the total body
weight.
Blood plasma - 8%
of the body weight.

Plasma compartment
Vd: around 5 L.
Very high molecular
weight drugs, ordrugs
that bind to plasma
proteins excesively
Example: heparin 4L (35)

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Extracellular fluid
Vd: between 4
and 14 L.
Drugs that have
a low molecular
weight but are
hydrophilic.
Example
Atracuronium 11
L (8-15)
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Vd equal or higher than total

body water
Diffusion to intracelullar fluid .
Vd equal to total body water.
Ethanol 38 L (34-41)
Alfentanyl 56 L (35-77)

Drug that binds strongly to

tissues. Vd higher than total
body water.
Fentanyl: 280 L
Propofol: 560 L
Digoxin:385 L

Why does Vd different for each drug?

The rate of delivery and potential

amount of drug distributed into
tissues depends on;
Cardiac output, Regional blood flow,
Capillary permeability and
tissue
volume.
Well-perfused organs (liver, kidney,
brain) initially receive most of the
drug
Lesser perfused: delivery to muscle,
most viscera, skin, and fat is

Distribution

determines
the
transport
of
drugs to their site of action, to other
sites,
and
to the organs of metabolism and
excretion.
Not uniform;
Difference in perfusion rates.
Penetrate - capillary endothelium.

Volume of Distribution (Vd )

values range from about 5% of body volume to as high as 400L.

The latter figure is much higher than anyones total volume, so Vd is an
artificial concept.
Importance - 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 also relates to whether a drug is Free / 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.
Useful for providing an estimate of dosage, it follows that it can help
estimate the amount of antidote to be given.
Indicate whether there is any value in trying to enhance elimination as,
for example, by dialysis.

Volume of distribution
Apparent and hypothetical volume in
which the drug is dispersed.
Dose
Vd
Plasma concentration

Why is it relevant?
To calculate the loading dose of a drug

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Volume of Distribution
Vd is helpful in the context of drug
monitoring.
Predicts whether the practice of drug
measurement in blood will have any
clinical value.
Psychotropic drugs such as

tranquilizers,
antidepressants, antipsychotics, mood-altering agents,
etc., create their effects by binding at

sites within the central nervous system.

Problem no 4
A physician wants to administer an
anesthetic agent at a rate of 2 mg/hr
by IV infusion. The elimination rate
constant is 0.1 hr 1, and the volume
of distribution (one compartment) is
10 L. What loading dose should be
recommended if the drug level to
reach 2 g/mL immediately?

Given, infusion rate =2mg/hr

elimination rate = 0.1 hr 1
volume of distribution =10L
Required concentration = 2 g/mL

Loading dose = Vd X Css

= 1000mL X 2 g/mL
= 2000 g
= 20mg
Here we can calculate LD using infusion rate and elimination rate
as well .

Reference books say the Vd of theophylline

is 0.5 L per kg of body weight.
What is the IV loading dose to give a serum
theophylline concentration of 12 mg/L in
a 62 kg man?
W

= C V

or

LD = Cp Vd

LD = (12 mg/L) (0.5 L/kg) (62 kg)

= 372 mg
we usually use mcg/mL (or ug/mL), which is the same thing as mg/L

Actually, theophylline for injection is available only as Aminophylline

(theophylline+ethylenediamine), which contains
80% theophylline. In this problem, we need
to give a larger weight of Aminophylline to
get the same weight of theophylline.
372 mg Theo
0.80

= 465 mg Amino

This gives us a loading dose

Question
What is the loading dose required for
drug A if;
Target concentration is 10 mg/L
Vd is 0.75 L/kg
Patients weight is 75 kg
Answer is on the next slide

Answer: Loading Dose of Drug A

Dose = Target Concentration x VD
Vd = 0.75 L/kg x 75 kg = 56.25 L
Target Conc. = 10 mg/L
Dose = 10 mg/L x 56.25 L = 565 mg
This would probably be rounded to 560 or
even 500 mg