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Noncompartmental Models
Noncompartmental Models
Introduction
• The noncompartmental approach for data analysis does
not require any specific compartmental model for the
system (body) and can be applied to virtually any
pharmacokinetic data.
• There are various noncompartmental approaches,
including statistical moment analysis, system analysis, or
the noncompartmental recirculatory model
• The main purpose of the noncompartmental approach is
to estimate various pharmacokinetic parameters, such
as systemic clearance, volume of distribution at steady
state, mean residence time, and bioavailability without
assuming or understanding any structural or mechanistic
properties of the pharmacokinetic behavior of a drug in
the body
Introduction
• In addition, many noncompartmental methods
allow the estimation of those pharmacokinetic
parameters from drug concentration profiles
without the complicated, and often subjective,
nonlinear regression processes required for the
compartmental models
• Owing to this versatility and ruggedness, the
noncompartmental approach is a primary
pharmacokinetic data analysis method for the
pharmaceutical industry
Statistical moment theory
• Suppose one could observe a single molecule,
from the time it is administered into the body ( t
= 0) until it is eventually eliminated ( t = tel )
• Clearly, tel is not predictable
• This individual molecule could be eliminated
during the first minute or could reside in the
body for weeks. If, however, one looks at a large
number of molecules collectively, their behavior
appears much more regular
• The collective, or mean time of residence, of all
the molecules in the dose, is called the mean
residence time (MRT).
Mean Residence Time (MRT)
• A mean time interval during which a drug
molecule resides in the body before being
excreted
MRT
AUMC
t C (t ).dt
0
AUC
C (t ).dt
0
AUC vs. AUMC
Estimating AUC and AUMC
Linear trapezoidal method
0 t1 t2 t3 tlast
Estimating AUC and AUMC
Linear trapezoidal method
• For samples until the last observed
concentration (t2<= tlast)
C2 C1
AUCt1t 2 (t 2 t1 )
2
t 2 C2 t1 C1
AUMCt1t 2 (t 2 t1 )
2
Estimating AUC and AUMC
Linear trapezoidal method
• For the last observed sample and infinity (t2= ∞)
Clast
AUCtlast
tlast Clast Clast
AUMCtlast
2
(Infusion time)
MRTiv MRTinfusion
2