Non compartmental model

• Compartmental methods consider the body to

consist of a finite number of interconnected, well-
mixed, and kinetically homogeneous compartments
(e.g., blood and other tissues/organs).
• Based upon this view, the pharmacokineticist
makes certain assumptions and develops models
based upon nonlinear regression analysis to
describe the PK of the drug.
• As a result of this approach, there is the potential
for variability in the output of the analysis from
one analyst to another, since the assumptions used
to build the PK model may be somewhat different.
 Non compartment model
• In contrast, noncompartmental analysis (NCA) methods
are model-independent, meaning they do not rely upon
assumptions about body compartments, and they tend to
provide more analyst-to-analyst consistency.
• In addition, an NCA relies almost exclusively upon
algebraic equations to estimate PK parameters, making
the analysis less complex than compartmental methods.
• As such, NCAs often prove faster and more cost-
efficient to conduct, especially when compared to more
complex compartmental analyses (e.g., where
compartmental models are applied to population
PK analyses that rely upon sparse sampling techniques)
• Compartmental methods boast key advantages for
characterizing PK across multiple studies, for
exploring PK variability due to intrinsic factors
(e.g., age, sex, race, renal impairment, hepatic
impairment) and extrinsic factors, and for informing
dosage adjustments based upon these factors.
• On the other hand, NCAs are typically favored for
characterizing PK within a single study, including
both final analyses and any interim analyses used to
make dose escalation decisions.
• In addition, NCA is the most commonly used
approach for establishing the initial exposure
characteristics of a drug prior to entry into the clinic
(i.e., during non clinical PK and toxicology studies).
 Moments:
• Moments of a function will play an essential role in estimating specific
pharmacokinetic parameters.
• The modern use of moments in the analysis of pharmacokinetic data and the
notions of noncompartmental or integral equation analysis can be traced to
• Yamaoka et al. (10) although these authors correctly point out that the
formulas were known since the late 1930’s.
• The moments of a function are defined below; how they are used will be
described later.
• Suppose C(t) is a real-valued function defined on the interval [0, ∞]; in this
lecture, C(t) will be used to denote a functional description of a set of
pharmacokinetic data.
• The zero, first and second moments of C(t), denoted 0 S , 1 S and 2 S are
defined:
 Zero moment curve
• AUC
• Calculated by trapezoid rule
 First moment curve (AUMC)
• The first moment is calculated as concentration
times time (Cp • t).
• The AUMC is the area under the concentration
times time versus time curve.
• Maybe best covered with an example. Consider a
drug given both by IV and oral administration.
• Both the AUC and AUMC were calculated using
the trapezoidal rule without making any assumption
concerning the number of compartments.
• The last segment for the AUMC curve is:
 2 moment curve
nd

• The second moment is calculated as

2
concentration times time square (Cp • t )
• Area is calculated by plotting the graph
• Last area is complicated in second curve so
neglected
• VRT = 2nd moment area / AUC
•
Calculate AUC ,AUMC , MRT,
Time (hr) Concentration (mg/L)
1 71
2 50
3 35
4 25
6 12
8 6.2
10 3.1