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Pharmacokinetic Models

The document discusses non-compartmental modeling and mean residence time approaches for analyzing drug concentration data over time without making assumptions about compartments. It describes how statistical moment theory can be used to study changes in drug concentrations in plasma or tissues. Mean residence time is defined as the average time a drug spends in the body before elimination. It can be calculated as the area under the first moment curve divided by the area under the concentration curve using non-compartmental analysis of plasma concentration-time data.

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83 views15 pages

Pharmacokinetic Models

The document discusses non-compartmental modeling and mean residence time approaches for analyzing drug concentration data over time without making assumptions about compartments. It describes how statistical moment theory can be used to study changes in drug concentrations in plasma or tissues. Mean residence time is defined as the average time a drug spends in the body before elimination. It can be calculated as the area under the first moment curve divided by the area under the concentration curve using non-compartmental analysis of plasma concentration-time data.

Uploaded by

varish
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Download as PPT, PDF, TXT or read online on Scribd
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Non-comparmental Model

 Absorption, distribution, and elimination


parameters are based on theory of statistical
moments
 Statistical moment theory provides a unique
way to study time – related changes in drug
concentration in the plasma and/or tissues
Synonymous

Mean Residence Time approach

Statistical Moment Approach

Non-compartmental analysis

2
Statistical Moments

• Describe the distribution of a random variable :


• location, dispersion, shape ...

Standard deviation

Mean Random variable values

3
MRT is defined as average amount of time
spent by the drug in the body before being
eliminated.
Mean Residence Time

Principle of the method: (1)


Entry : time = 0, N molecules
 Evaluation of the time each molecule of a
dose stays in the system: t1, t2, t3…tN

 MRT = mean of the different times

t1 + t2 + t3 +...tN
MRT =
N

Exit : times t1, t2, …,tN

5
Mean Residence Time

Principle of the method : (2)

 Under minimal assumptions, the plasma


concentration curve provides information on the
time spent by the drug molecules in the body

6
Mean Residence Time

Principle of the method: (3)


Entry (exogenous, endogenous)

Central
compartment recirculation
(measure) exchanges

Exit (single) : excretion, metabolism

Only one exit from the measurement compartment


First-order elimination : linearity

7
Mean Residence Time

Principle of the method: (4)


• N molecules administered in the system at t=0
• The molecules eliminated at t1 have a residence time in the system
equal to t1
Consequence of linearity
 AUC is proportional to N
C tot

 Number n1 of molecules eliminated at t1+ t is


proportional to AUCt:
C1
AUCt C(t1) x t
n1 = XN = XN
AUCtot AUCtot
t1 (t)
8
Mean Residence Time

Principle of the method: (5)


C Cumulated residence times of molecules
eliminated during t at :
C1
Cn t1 : t1 x C(1) x tx N n1
AUCTOT
C(n) x t
t1 tn (t) tn : tn x xN
AUCTOT

C1 x t x N Cn x t x N
MRT = t1xtn x N
AUCTOT AUCTOT

9
Mean Residence Time

Principle of the method: (5)


C1 x t x N Cn x t x N
MRT = t1xtn x N
AUCTOT AUCTOT

MRT = t1xC1 x ttn x Cn x t AUCTOT

 ti x Ci x t  t C(t) t AUMC
MRT = = =
AUCTOT  C(t) t AUC

10
Statistical Moment Approach


  C t  dt
n
• n-order statistical moment t
0
 
  C t  dt   C t  dt  AUC
0
• zero-order : t
0 0

• one-order :  t  C t  dt  AUMC
0
11
MRT represents half-life
It can be obtained by
MRT= AUMC/AUC
 AUMC = Area Under First Moment Curve
AUC = Area Under the Zero Moment
Curve.

 t1 tn 
AUMC   t  C (t )dt   t  C (t )dt   t  C (t )dt   t  C (t )dt
0 0 t1 tn

 t1 tn 
AUC   C (t )dt   C (t )dt   C (t )dt   C (t )dt
0 0 t1 tn

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