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What is the rationale for using linear trapezoidal method for
noncompartmental AUC calculation versus using the log linear method?
I am analyzing data from single dose, 1.0 hr IV infusion, with data
points at pre-infusion, 0.5 hr and 1.0 hr and then multiple samples
out to 24 hr.
Any thoughts on most appropriate method for AUC determination using
a noncompartmental analysis?
Drug disposition is probably described by a 2-compartmental model
(fitting will come later).
Dave
[Have a look at:
Yeh and Kwan (Yeh, K.C. and Kwan, K.C. 1978 "A comparison of numerical
integrating algorithms by trapezoidal Lagrange and spline
approximation", J. Pharmacokin. Biopharm., 6, 79-98) and
Purves (Purves, R.D. 1992 "Optimum numerical integration methods for
estimation of area under the curve (AUC) and area under the moment
curve (AUMC)", J. Pharmacokin. Biopharm., 20, 211-226) - db]
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The following message was posted to: PharmPK
Dave:
David's references are classics and well worth the read. I had heard
that many use trapezoidal up, log-trapezoidal down, but other use only
trapezoidal. The reason for the use of only trapezoidal is that there
is no ambiguity about when to convert from one method to another. I
would be interested to hear what folks with more FDA experience have
to say about the choice of algorithms.
I remember the existence of an old DOS program called LAPLACE that
gave options on which algorithms to use and when to start and stop them.
Paul
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Dave,
Linear trapezoidal rule overestimates the area during the descending
phase when the differences in the time points are large. Hence a
combination of linear trapezoidal during ascending phase and log
linear method during descending phase is recommended for estimating
AUC. WinNonlin provides this option of Linear up/Log down in Model
options/NCA settings.
Ref
PK PD Data Analysis: Concepts & applications by J Gabrielsson and D.
Weiner
Best
Ganesh Mugundu
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The linear trapezoidal rule method is commonly used for the estimation
of the area under the plasma level-time curve. Error analyses are
performed when the method is used in first-order absorption and first-
order elimination kinetics in the one-compartment system.
It is found that significant underestimations and overestimations in
area during the absorption phase and postabsorption phase,
respectively, can occur when the method is improperly used. During the
exponential postabsorption phase the relative error is only a function
of the ratio (n)of the time interval over the half-life of the two
plasma data points in the interval. The error from the linear
trapezoidal rule method at n=0.5 is about 1%. The error increases to
15.5% and 57.1 % when nis increased to 2 and 4, respectively.
It is recommended that for most absorption studies the linear
trapezoidal method be used for prepeak and plateau plasma data and the
logarithmic trapezoidal method for postpeak plasma data.
Regards,
Prashant Nigade
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The following message was posted to: PharmPK
Dear Paul,
You wrote:
> David's references are classics and well worth the read. I had heard
> that many use trapezoidal up, log-trapezoidal down, but other use
only
> trapezoidal. The reason for the use of only trapezoidal is that
there is
> no ambiguity about when to convert from one method to another.
There is some references for this topic (David Bourne also listed a
few in
an added note to Dave's question):
Proost JH. Wagner's exact Loo-Riegelman equation: the need for a
criterion
to choose between the linear and logarithmic trapezoidal rule. J Pharm
Sci
1985;74:793-794.
I will send a pdf of this paper upon request.
This paper was cited by John G. Wagner in his book 'Pharmacokinetics
for the
Pharmaceutical Scientist' (Technomic publishing co, Lancaster, 1993
(ISBN
1-56676-032-1), pp 185-186.
best regards,
Hans Proost
Johannes H. Proost
Dept. of Pharmacokinetics and Drug Delivery
University Centre for Pharmacy
Antonius Deusinglaan 1
9713 AV Groningen, The Netherlands
Email: j.h.proost.aaa.rug.nl
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