Tissue-blood partition coefficients, QSAR

Tissue Blood Partition Coefficients QSAR Models... 

Ruark, C.D., Hack, C.E. Sterner, T.R., Robinson, P.J., Gearhart, J.M. (2008). Quantitative structure activity relationship (QSAR) for extrapolation of tissue/blood partition coefficients of nerve agents across species. DTRA 16th Biennial Medical Chemical Defense Bioscience Review June 1-6, 2008, Hunt Valley, MD. 

Knaak et al. (2008) reviewed the literature pertaining to in vitro methods for developing tissue blood partition coefficients for PBPK models. The experimental work of Jepson et al. (1992,1994) is significant. Ultrafiltration was used to develop tissue saline and tissue blood partition coefficients. No new studies of this nature were found during the preparation of this review on pyrethroids. Automated laboratory methods are still needed and must be developed to insure the partition coefficients obtained firom the use of mechanistic or QSAR models are reasonable (Payne and Kenny 2002 Rowland, personal communication). 

Knaak et al. (2008) reviewed the nonlinear QSAR equation developed by Zhang (2005) and the QSAR model developed by Liu et al. (2005a) for predicting tissue blood partition coefficients. To our knowledge, neither the QSAR equations nor models are available in the form of ready-to-use programs for obtaining partition... 

Results in Table 31.3 indicate that the combination of TS and TC descriptors resulted in a highly predictive RR model = 0.895) the addition of three-dimensional and QC indices to the set of independent variables did not result in significant improvement in model quality. It may be noted that we have observed such results for various other physicochemical and biological properties including mutagenicity [25,54], boiling point [55], blood air partition coefficient [37], tissue air partition coefficient [46], etc. [24,30,45,56]. Only in limited cases, e.g., halocarbon toxicity [12], the addition of QC indices after TS and TC parameters resulted in significant improvement in QSAR model quality. 

Katritzky A.R., Kuanar, M., Fara, D.C., Karelson, M., Acree, W.E., Jr, Solov ev, VP. and Varnek, A. (2005) QSAR modeling of blood air and tissue air partition coefficients using theoretical descriptors. Bioorg. Med. Chem., 13, 6450-6463. 

EXPERIMENTAL AND QSAR METHODOLOGIES TO PREDICT BLOOD AND TISSUE PARTITION COEFFICIENTS... 

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