Volume of distribution

Dr.Jeevan JacobJunior Resident

Dept. of Pharmacology

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Introduction

Compartments

-One Compartment Model

-Two compartment Model

-Multi Compartment Model

Volume of Distribution(Vd)

-Calculation

-Applications

-Factor affecting Vd

Conclusion

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KINETICS- The temporal and spatial distribution of a substance in a system.

• Temporal: When in the system

• Spatial: Where in the system

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PHARMACOKINETICS- The temporal and spatial distribution of a drug in a system.

Study of rates of

Absorption,

Metabolism, Excretionof a drug in quantifiable mathematical forms.

Distribution

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It is the hypothetical space bound by unspecified membrane across which drugs are transferred

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• We assume our body as single or multiple compartments in which drug resides in a dynamic state for a short period of time

• Volume size of compartment is constant

• Compartment is well stirred and therefore the drug is distributed uniformly throughout

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• The model is an open system since drug is

eliminated from the system.

• The amount of drug in the body is the sum

of drug present in the compartments.

• Parameters are kinetically determined from

the data.

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Blood

(Vd)

Ka

Input

kel

Output

Ka and Kel can be calculated from slope of Plasma Conc. – time curve

c1

c2

t1 t2

Slope = log C1 – log C2t1 – t2

Plasma conc.

time

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When the drug is distributed at very fast rates, it can be assumed that the drug has reached equilibrium state in all fluid spaces and tissues instantaneously, hence the kinetic behavior of drug is said to follow a one compartmental Model

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In Two compartment Model, the body is resolved into Central and Peripheral Compartments

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Heart, Lungs, Kidneys, liver, Brain etc are considered as central compartments

Whereas skin, fat, muscles are considered as peripheral compartments

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α ( Distribution phase)

β (Elimination Phase)

Plasma conc.

time

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Alpha – occurs rapidly and reach Equilibrium with Central and Peripheral compartments.

Beta – starts after alpha phase and it indicates elimination from central compartment

Central and Peripheral Compartments may vary from drug to drug. Eg: Brain act as Central compartment for Thiopental but as Peripheral compartment for aspirin

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When the net transfer between two Compartment is zero then it is said to have achieved state of equilibrium

Ka = Kel

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“It is the apparent volume to which drug would have to distribute to achieve measured concentration.”

From Plasma conc.- time curve, only the fluid volume in which the drug distributed can be calculated. Here we assume that the drug is distributed uniformly throughout the compartments but it is not the case as it does not reflect real body fluid volume.

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So we refer it as apparent volume of distribution and is only a PK parameter that represent the volume or size of compartment in which it would have to be uniformly distributed in order to give the observed plasma concentration if no elimination occurred

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1. One Compartment Model

Vd = Dose administered IV

Plasma Concentration

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2. Two compartment model

Vd 1 = Distribution in Central Compartment

Vd 2= Distribution in peripheral compartment

Total Vd= Vd1 + Vd2

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1. Loading dose can be estimated

2. Clearance can be calculated

3. Total amount of drug present in the body can be determined

eldkVCl

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1. Extra cellular Fluid- In children ECF : TBW is large, so Vd is increased hence dose adjustments are required

2. Tissue Perfusion – decreased perfusion implies decreased Vd

3. Plasma protein binding- High Plasma protein binding decreases Vd. Eg. Phenyl butazone( 96% PP bound, Vd = 97 ml/kg)

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4. Water Soluble drugs have low Vd.Eg. Gentamycin (vd = 110 ml/kg)

5. Lipid soluble drugs have high VdEg. Thiopental( vd = 2300 ml/kg)

6. Acidic drugs have low Vd.Eg. Valproic acid,(Vd = 220 ml/kg)

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7. Pathological condition. Eg. In edematous condition, water soluble drugs have high volume of distribution

8. Tissue binding. High Vd with higher tissue binding Eg. Chloroquine ( Vd – 15000 litre)

9.Low molecular weight drugs have high Vd

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Pharmakokinetics is the study of rates of absorbtion, distribution, metabolism and excretion of drug.

We use different compartmental models to explain these parameters

Apparent volume of distribution is thus explained using Compartment models

It is the volume that would be required to contain all drug in the body if it was distributed at concentration measured in the plasma

Essentials of Medical Pharmacology, 7th Ed. KDT

Textbook of Biopharmaceutics and Pharmacokinetics 1st Ed. Subramnayam

Printed Notes provided by The Faculty, Dept. Of Pharmacology, Govt. medical College, Calicut

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