Convenient Nonlinear Model for Predicting the Tissue/Blood Partition Coefficients of Seven Human Tissues of Neutral, Acidic, and Basic Structurally Diverse Compounds

Abstract

In this work, the tissue/blood partition coefficients of seven human tissues were calculated using a nonlinear regression analysis. The dataset contained 80 structurally diverse compounds distributing into the brain, kidney, muscle, lung, liver, heart, and fat, whose acidic and basic properties were also considered by introducing the three possible forms of the compound in the human body (neutral, cationic, and anionic forms). A total of 248 data points were there in the training set (eq 5: r = 0.877, s = 0.352; eq 6: r = 0.869, s = 0.362) and 49 data points in the testing set (eq 5: r = 0.844, s = 0.342; eq 6: r = 0.860, s = 0.311). It was also concluded that the same state (neutral, cation, and anion) of a compound has essentially identical partition coefficients between the same tissue composition and the blood in these tissues. Only the different content of the three tissue compositions (lipid, protein, and water) lead to the different partition coefficient in different tissues, which offered a significant conclusion for the drug's distribution research.

MR measurement of blood flow in the parotid gland without contrast medium: a functional study before and after gustatory stimulation

“…According to the extended Bloch equation, the blood flow in the tissue also depends on the blood/tissue partition coefficient l. It is known that the magnitude of the partition coefficient is modulated by the volume or weight fraction of the tissue composition (44). In a simplified approach mainly focusing on the assessment of stimulation-related differences in tissue blood flow, l was set to 100 mL/100 g. This simplification does not consider labeled blood which has already left the image slice before signal recording.…”

Synthesis and bio‐evaluation of Tc‐99 m‐labeled fatty acid derivatives for myocardial metabolism imaging

“…1). Log P of shorter chain fatty acid is slightly lower than that of longer chain acid which indicates that the shorter chain fatty acid is more hydrophilic [19,20] ( Tc-labeled complexes (1c, 2c, 3c, 4c) are stable in Kunming mice serum at 37°C (Fig. 2).…”

Prediction of Distribution of Neutral, Acidic and Basic Structurally Diverse Compounds Between Blood and Brain by the Nonlinear Methodology

“…The calculation of solvation free energies ( Gw) for all of the molecules were performed using the AMSOL 6.8 program. The solvation free energies in water were computed with the AM1-SM 5.4A solvation model [16]. Parameters for describing the cationic and anionic forms of the compounds were also obtained by the methods mentioned above.…”

“…The brain/blood partition coefficients logBB were taken from several references [10,[14][15][16][17][18]. The molecular structures and the pKa values were looked up with the program Scifinder Scholar (Version 2006) offered by American Chemical Society, the values on the program were calculated using Advanced Chemistry Development (ACD/Labs) Software V8.…”

“…Our previous work had also made progress in prediction of logBB [14,15,16]. Different from above studies, our work made use of nonlinear equations, which would be listed in detail as follow, and the most important, the equations not only could give results of logBB prediction, but also could express the distribution of the compounds into the three predominant tissue compositions, lipid, protein and water.…”