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12 Drug Distribution

This document discusses the pharmacokinetic process of drug distribution. It defines distribution as the reversible transfer of drugs between compartments like the bloodstream and tissues. Several factors affect a drug's distribution, including its physicochemical properties, blood flow to tissues, and binding to plasma proteins or tissue macromolecules. Physiological barriers like the blood-brain barrier also influence distribution. The volume of distribution is introduced as the hypothetical volume required to account for the total amount of drug in the body based on its plasma concentration. Understanding distribution and volume of distribution is important for calculating drug dosing, estimating elimination, and predicting half-life.

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Mahreen Noor
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20 views

12 Drug Distribution

This document discusses the pharmacokinetic process of drug distribution. It defines distribution as the reversible transfer of drugs between compartments like the bloodstream and tissues. Several factors affect a drug's distribution, including its physicochemical properties, blood flow to tissues, and binding to plasma proteins or tissue macromolecules. Physiological barriers like the blood-brain barrier also influence distribution. The volume of distribution is introduced as the hypothetical volume required to account for the total amount of drug in the body based on its plasma concentration. Understanding distribution and volume of distribution is important for calculating drug dosing, estimating elimination, and predicting half-life.

Uploaded by

Mahreen Noor
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd
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PHARMACOKINETIC

DISTRIBUTION OF DRUGS

Dr. Shaukat Hussain Munawar (PhD)


Assistant Professor
Pharmacology & Toxicology
CUVAS, Bahawalpur
LEARNING OBJECTIVES
 What is drug distribution?
 What are the factors that affect distribution of drugs in
the body and how?
 Barriers to Drug Distribution?

 What is volume of distribution (Vd)?

 How Vd is determined?

 What is importance of Vd?


DRUG DISTRIBUTION

Distribution may be defined as a process by which drugs reversibly


leave the blood stream and enter the extra-vascular fluid and tissues.
OR

“It is reversible transfer of drugs between one compartment and another


(”between blood & extravascular fluids & tissues)'

 Distribution is an important pharmacokinetic process as it determines


the transport of drugs to their site of action and to the organs of
metabolism and excretion.

 Distribution of a drug is not uniform throughout the body because of


difference in perfusion rates.
LOCUS OF ACTION TISSUE
“RECEPTORS” RESERVOIRS
Bound Free Free Bound

ABSORPTION Free Drug EXCRETION

SYSTEMIC
Bound Drug CIRCULATION

BIOTRANSFORMATION
FACTORS AFFECTING DRUG
DISTRIBUTION
I. Physicochemical characteristics of drug
 Lipid solubility
 Molecular weight
II. Blood flow to the tissues
III. Binding of drug to
 Plasma proteins
 Tissue macromolecules
IV. Physiological Barriers
1) Simple capillary endothelial barrier (size < 600 daltons diffuse)
2) Simple cell membrane barrier (Lipophillic)
3) Blood brain barrier
4) Blood CSF barrier
5) Blood placental barrier
I. PHYSICOCHEMICAL PROPERTIES OF DRUG

 Almost all drugs having molecular size less than 500 to 600 Da
easily cross the capillary membranes to penetrate into the
extracellular fluids (except in CNS)

 However, passage of drugs from the ECF into the cells is a


function of molecular size, degree of ionization and
lipophilicity of the drug.
 According to the pH-partition hypothesis:

 Ion Traping

Weak bases tend to accumulate in milk since the pH of milk


is slightly acidic (pH 6.5 to 6.8) to the blood.
II. BLOOD FLOW TO THE TISSUES

 Better perfused tissues achieve greater drug


concentrations

 Poorly perfused tissues have lower drug concentration


III. BINDING OF DRUGS TO
MACROMOLECULES
 Plasma proteins
 Protein bound drugs can not escape capillary
endothelium
 Only free drug can distribute outside of vascular
space
 Acidic drugs bind to albumin
 Basic drugs bind to α1-acid glycoprotein
IV-PHYSIOLOGICAL BARRIERS
1) Simple capillary endothelial barrier (size < 600 daltons
diffuse)
2) Simple cell membrane barrier (Lipophillic)
3) Blood brain barrier
4) Blood CSF barrier
5) Blood placental barrier
Blood Brain Barriers (BBB)

Tight junctions b/w capillary endothelium in brain limit bulk


flow of macromolecules

Drug penetration highly depends upon lipid solubility (Only


Lipid soluble & unionized drugs penetrate easily to brain).

• e.g. volatile anaesthetics etc.


BLOOD BRAIN BARRIER
 Maternal & fetal blood vessels
are separated by a number of
tissue layers made of fetal
trophoblast , basement membrane
& endothelium -placental barrier
 Drugs having molecular size
less than 1000 D and moderate
lipid solubility cross the placental
barrier

21
VOLUME OF DISTRIBUTION (VD)
“Hypothetical volume of fluid into which a drug is
dispersed”
HOW VD IS CALCULATED?
D = Vd x C
or
Vd = D/C

where C = the plasma concentration of the drug and D =


the total amount of drug in the body.

 For example, if 25 mgs of a drug (D = 25 mg) are


administered and the plasma concentration is 1 mg/L,
then Vd = 25 mg/1mg/L = 25 L
WHY VD IS IMPORTANT?
 Vd is used for:
 calculating dose of a drug
 estimating elimination
 estimating half life
REFERENCES
 Goodman & gillman’s 12th edition, the
pharmacological basis of therapeutics
 Principles of pharmacology 2nd by H. L. Sharma &
K .K. Sharma
 Biopharmaceutics and pharmacokinetics a treatise 2nd
edition by D. M. Brahmankar and Sunil B. Jaiswal
THANK YOU
Any Question???

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