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I did an experiment for the pharmacokinetic study of our compound recently.
In my study, I found that if I calculate the PK parameters with the C-T curve from a same rat, the blood elimination half-life of the compound is about 4.5 hours. However, if I use the data obtained from a serial rats (from distribution study, 6 rats at each time point), the blood elimination half-life is about 1.5 hours.
I'm very grateful if someone can give me some advices on how to explain the difference between these two calculation methods.
Thank you very much!
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I am not surprised at all at your result. Have a look at our paper of some 20 years ago, Noninvasive Estimation of Bound and Mobile Platinum Compounds in the Kidney Using a Radiopharmacokinetic Model. R. R. Brechner, D. Z. D'Argenio, R. Dahalan and W. Wolf, J. Pharm. Sci., 75, 873-877, 1986, where we documented that key parameters will depend significantly on the unique physiological (or pathophysiological) characteristics of each individual. What you have to look at are the mechanisms involved: is your compound metabolized/bound in plasma?; is the elimination primarily renal of the compound itself or of one of its metabolites?; is your compound metabolized in the liver or in other tissues?.
There is a cartoon in Remington that illustrates how statistical considerations can be misleading for single individuals: a duck is sitting exactly between two bullet holes, and the legend says: on the average, the duck is dead.
-- Professor Walter Wolf, Ph.D.
Distinguished Professor of Pharmaceutical Sciences
Director, Pharmacokinetic Imaging Program
Department of Pharmaceutical Sciences, School of Pharmacy
Chair, Biomedical Imaging Science Initiative
University of Southern California
1985 Zonal Ave., Los Angeles, 90089-9121
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