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

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 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

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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

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 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)
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 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

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 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

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 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
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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