- On 14 Sep 2005 at 15:54:13, "Dan Lu" (lu.168.-a-.osu.edu) sent the message

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Dear all,

I have a question about how to compare the two plasma-concentration

curves from PK study on mice.

We have two groups, with seven time points on each curve. The data

from three mice were averaged for each time point.

As you know, each mice will be euthanized for each data point, thus

it is not the repeated measurement on one subject.

So how to compare the difference of the two curves? Can I run some

statistical test and conclude there is significant difference between

the two curves?

Or I can only get some parameters such as AUC, Clearance? You know,

even I got those parameters, I can not do any statistical analysis.

Thanks a lot.

Dan Lu

Division of Pharmaceutics

the Ohio State University

Columbus, Ohio 43210

614-688-3597 - On 14 Sep 2005 at 16:48:33, "Shoaf, Susan" (Susan.Shoaf.at.otsuka.com) sent the message

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The following message was posted to: PharmPK

Hi Dan,

Try Wang J. Optimal design for linear interpolation of curves.Stat

Med. 2001 Aug 30;20(16):2467-77.

This paper proposes optimal designs that minimize the mean squared

error of linear interpolation. Optimal designs for three situations

are considered. The first... The third situation is destructive

sampling where estimating the average curve is the main purpose. In

the first situation, the design results in the best linear

interpolation when the variance is constant. For the destructive

sampling design, an algorithm based on approximations is proposed.

Mayo and Buchsbaum A robust summarize-regress procedure for tissue-

specific pharmacokinetics

J Biopharm Stat. 2000 May;10(2):251-64

Bialer and Ruberg Randomization tests for assessing the equality of

area under curves for studies using destructive sampling J Appl

Toxicol. 1996 Sep-Oct;16(5):391-5.

Mager and Goller Resampling methods in sparse sampling situations in

preclinical pharmacokinetic studies. J Pharm Sci. 1998 Mar;87(3):372-8.

Vandenhende F, Comblain M, Delsemme MH, Dewe W, Hoffman WP, Boulanger

B. Construction of an optimal destructive sampling design for

noncompartmental AUC estimation J Pharmacokinet Biopharm. 1999 Apr;27

(2):191-212

Nedelman JR, Gibiansky E. The variance of a better AUC estimator for

sparse, destructive sampling in toxicokinetics. J Pharm Sci. 1996 Aug;

85(8):884-6

I used "destructive sampling" pharmacokinetic as search words in PubMed.

Susan Shoaf, Ph.D.

Sr. Pharmacokineticist

Clinical Pharmacology, Clinical Development

Otsuka Maryland Research Inst.

Rockville, MD

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