MULTI-COMPARTMENT
MODEL IV BOLUS
Sufian Khan
#06332013065
INTRODUCTION
• Contrary to the mono-exponential decay in the
simple one-compartment model, most drugs
given by IV bolus dose decline in a biphasic or
triphasic fashion, that is, plasma drug
concentrations rapidly decline soon after IV
bolus injection, and then decline moderately.
• These models were developed to explain the
observation that after rapid IV injection the
plasma level time curve does not decline
linearly as a single first order rate process
• Multi-compartment models provide answers to
questions such as how much drug accumulates
in the tissue compartment?
INTRODUCTION
• Nonlinear plasma drug level–time decline occurs because
some drugs distribute at various rates into different tissue
groups.
• Because of all these distribution factors, drugs will generally
concentrate unevenly in the tissues, and different groups of
tissues will accumulate the drug at very different rates.
• Kinetic analysis of a multi-compartment model assumes that
all transfer rate processes for the passage of drug into or out of
individual compartments are first-order processes.
TWO-COMPARTMENT OPEN MODEL
• The plasma level–time curve for a drug that
follows a two-compartment model shows that the
plasma drug concentration declines
biexponentially as the sum of two first-order
processes— distribution and elimination.
•In this model, the drug distributes into two
compartments, the central compartment(highly
perfuse tissues), and the tissue, or peripheral,
compartment(Low perfuse tissues).
• The plasma level–time curve for a drug that
follows a two-compartment model may be divided
into two parts, (a) a distribution phase and (b) an
elimination phase.
TWO-COMPARTMENT OPEN MODEL
• Although drug elimination and distribution occur
concurrently during the distribution phase, there is a
net transfer of drug from the central compartment to
the tissue compartment because the rate of
distribution is faster than the rate of elimination.
•.The fraction of drug in the tissue compartment
during the distribution phase increases up to a
maximum in a given tissue, whose value may be
greater or less than the plasma drug concentration.
• At maximum tissue concentrations, the rate of drug
entry into the tissue equals the rate of drug exit from
the tissue.
TWO-COMPARTMENT OPEN MODEL
• The fraction of drug in the tissue compartment is now in equilibrium
(distribution equilibrium) with the fraction of drug in the central
compartment, and the drug concentrations in both the central and tissue
compartments decline in parallel and more slowly compared to the
distribution phase. This decline is a first-order process and is called the
elimination phase or the beta (b) phase.
CATEGORIES OF TWO-COMPARTMENT MODEL
• Depending upon the compartment from which elimination is carried out, it
has three categories:
• In the model depicted above, k12 and k21 are first-order rate
constants that govern the rate of drug distribution into and out of the
tissues and plasma. Also called microconstants or transfer constants.
Mathematical Expression
The rate of change in drug concentration in central and tissue compartment
is given by:
(1)
(2)
The relationship between the amount of drug in each compartment and the
concentration of drug in that compartment is shown by Equations (3) and
(4):
(3) where
Dp = amount of drug in the central compartment,
Dt = amount of drug in the tissue compartment,
Vp = volume of drug in the central compartment
(4) Vt = volume of drug in the tissue compartment.
Mathematical Expression
Putting values from (3) and (4) into (1) and (2):
(5)
(6)
Solving Equations (5) and (6) using integration will give Equations (7) and
(8), which describe the change in drug concentration in the blood and in the
tissue with respect to time:
(7) Dp0 = dose given intravenously
t = time after administration of
dose, and a and b are constants
(8) that depend solely on k12, k21,
and k10
Mathematical Expression
The amount of drug remaining in the plasma and tissue compartments at
any time may be described realistically by Equations (9) and (10).
(9)
(10)
Lastly,
The transfer rate constants relate the amount of drug being transferred per
unit time from one compartment to the other and there values cannot be
determined by direct measurement, but they can be estimated by a graphic
method. a and b are also called hybrid-rate constants given by relation:
(11)
(12)
THREE
COMPARTMENT
OPEN MODEL
ZAHID ALI
06331913066
INTRODUCTION
● The three compartment open model describes drug distribution and elimination
in the body.
● It divides the body into three compartments: central, peripheral, and deep.
● This model is used in pharmacokinetics to understand how drugs move through
the body.
CENTRAL COMPARTMENT
● The central compartment includes the blood and highly perfused organs.
● It is the primary site for drug absorption and elimination.
● Drug concentration in this compartment is typically measured to monitor
therapy.
● .
● Above equation describing the rate of change of drug concentration in central
compartment.
PERIPHERAL AND DEEP TISSUE COMPARTMENT
● The peripheral compartment consists of less well-perfused tissues such as muscle
and fat.
● The deep tissue compartment includes tissues like bone and adipose tissue
where the drug penetrates slowly.
● Drugs move between compartments at specific rate constants. e.g, k12,k21,k13,k31,
k10.
● Equations describing the rate of change of drug concentration in each
compartment.
TWO COMPARTMENT
EXTRAVASCULAR MODEL
AHTISHAM ANWAR
06332013036
TWO COMPARTMENT EXTRAVASCULAR MODEL
The model can be depicted as follows:
K12
ka 1 2
Central compartment Peripheral compartment
K21
For a drug which enters the body by first order absorption process &
distribution to two Compartment model, the rate of change of drug
concentration in Cc is described by 3 exponents
➢ Absorption exponent
➢ Elimination exponent
➢ Distribution exponent
The plasma concentration at time t, is given by
C = Ne-Kat + Le-αt + e-βt
Where, N, L & M are coefficient
The 3- exponents can be resolved stepwise by method of residual. Absorption
rate constant Ka can be determined by the method of Residual and Loo-
Riegelman method.
Determination of absorption rate constant Ka by Loo-
Riegelman method using 2COM
After oral administration of a dose of a drug that exhibits two compartment model
kinetics, the amount of drug absorbed is calculated as the sum of the amt. of
drug in the central compartment (XC ), XP (tissue compartment) and amt. of drug
eliminated by all routes XE
XA=XC+XP+XE 1
Each of these terms, may be expressed in terms of kinetic constant & plasma
drug concentration as follows
IMPORTANCE
➢ Enhanced Understanding of Drug Dynamics
• Central Compartment
Typically represents the bloodstream and organs with high blood flow,
where the drug is initially distributed.
• Peripheral Compartment
Represents tissues and organs where the drug may distribute more
slowly
➢ Improved Accuracy in Pharmacokinetic Predictions
Compared to a simpler one-compartment model, the two-compartment
model provides a more accurate description of the pharmacokinetics of
many drugs, particularly those with complex distribution phases
➢ Better Dose Optimization
By modeling the drug concentrations in both compartments, healthcare
providers can optimize dosing regimens to achieve therapeutic
concentrations while minimizing toxicity.
➢ Tailored Therapeutic Strategies
Understanding the distribution in both compartments helps in designing
drugs with desired characteristics, such as sustained release formulations
or targeted delivery systems.
➢ Application to Various Fields
Besides pharmacokinetics, the two-compartment model is used in
toxicology, physiology, and other fields where understanding the
distribution of substances within the body is critical.
Thank you