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I know that the partition coefficeint value can be predicted in
vitro. But if I do have the tissue concentration vs. time data, will
the tissue AUC be a good way to estimate this P value? If yes, then
how to calculate the tissue AUC? Thank you very much,
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The following message was posted to: PharmPK
>"... if I do have the tissue concentration vs. time data, will
>the tissue AUC be a good way to estimate this P value?...">>
The short answer is: no, unless you reached a steady-state (e.g.,
using continuous infusion, osmotic pump, etc.).
Below are some relevant references.
Janusz Z. Byczkowski, Ph.D.,D.Sc.,D.A.B.T.
212 N. Central Ave.
Fairborn, OH 45324
JZB Consulting web site: http://members.aol.com/JanuszB/consult.htm
Gargas ML, Burgess RJ, Voisard DE, Cason GH, Anderson ME. (1989).
Partition coefficients of low-molecular-weight volatile chemicals in
various liquids and tissues. Toxicol. Appl. Pharmacol. 97:87-99.
Jepson GW, Hoover DK, Black RK, McCafferty JD, Mahle DA, Gearhart JM.
(1994). A partition coefficient method for non-volatile and
intermediate volatility chemicals in biological tissues. Fund. Appl.
Pelekis M, Gephart LA, Lerman SE. (2001). Physiological model-based
derivation of the adult and child pharmacokinetic intraspecies
uncertainty factors for volatile organic compounds. Regulat. Toxicol.
Pharmacol. J. 33:12-20.
Pelekis M, Poulin P, Krishnan K. (1995). An approach for
incorporating tissue composition data into physiologically based
pharmacokinetic models. Toxicol. Ind. Health 11:511-522.
Poulin P, Krishnan K. (1995). A biologically-based algorithm for
predicting human tissue: blood partition coefficients of organic
chemicals. Human Exp. Toxicol. 14: 273-280.
Poulin P, Krishnan K. (1996). A tissue composition-based algorithm
for predicting tissue:air partition coefficients of organic
chemicals. Toxicol. Appl. Pharmacol. 136:126-130.
[Curve fitting the Cp and Ct value could be possible, resulting in
values for P (R) - db]
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