Air to lung partition coefficients for volatile organic compounds and blood to lung partition coefficients for volatile organic compounds and drugs

被引:47
作者
Abraham, Michael H. [1 ]
Ibrahim, Adam [1 ]
Acree, William E., Jr. [2 ]
机构
[1] UCL, Dept Chem, London WC1H 0AJ, Middx, England
[2] Univ N Texas, Dept Chem, Denton, TX 76203 USA
关键词
volatile organic compounds; drugs; lung; blood-lung; plasma-lung; partition coefficients; linear free energy relationship; Abraham equation; hydrogen-bond;
D O I
10.1016/j.ejmech.2007.04.002
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Values of in vitro gas to lung partition coefficients, K(lung), of VOCs have been collected from the literature. For 44 VOCs, application of the Abraham solvation equation to log K(lung) yielded a correlation with R(2) = 0.968 and S.D. = 0.25 log units. Combination of the log K(lung) values with log K(blood) values leads to in vitro blood to lung partition coefficients, log P(lung) for 43 VOCs; an Abraham solvation equation correlated these values with a very poor R(2) = 0.262 but with a very good S.D. = 0.190 log units. Values of in vivo log P(lung) for 80 drugs were collected, and were correlated with R(2) = 0.647 and S.D. = 0.51 log units. When the 109 P(lung) values for VOCs and drugs were combined, an Abraham solvation equation could correlate the 123 compounds with R(2) = 0.676 and S.D. = 0.43 log units. Division of the 123 compounds into a training set and a test set, showed that the training equation could predict log P(lung) values with an average error of 0.001 and a standard deviation of 0.44 log units; for drugs in the combined test set the average error was 0.02 and the standard deviation 0.43 log units. (c) 2007 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:478 / 485
页数:8
相关论文
共 62 条
[1]   HYDROGEN-BONDING .30. SOLUBILITY OF GASES AND VAPORS IN BIOLOGICAL LIQUIDS AND TISSUES [J].
ABRAHAM, MH ;
WEATHERSBY, PK .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1994, 83 (10) :1450-1456
[3]   Air to blood distribution of volatile organic compounds: A linear free energy analysis [J].
Abraham, MH ;
Ibrahim, A ;
Acree, WE .
CHEMICAL RESEARCH IN TOXICOLOGY, 2005, 18 (05) :904-911
[4]   Human skin permeation and partition: General linear free-energy relationship analyses [J].
Abraham, MH ;
Martins, F .
JOURNAL OF PHARMACEUTICAL SCIENCES, 2004, 93 (06) :1508-1523
[5]   Determination of sets of solute descriptors from chromatographic measurements [J].
Abraham, MH ;
Ibrahim, A ;
Zissimos, AM .
JOURNAL OF CHROMATOGRAPHY A, 2004, 1037 (1-2) :29-47
[6]  
ABRAHAM MH, 2002, EUROQSAR 2002 DESIGN, P5
[7]  
ABRAHAM MH, IN PRESS J MED CHEM
[8]   Partition of compounds from gas to water and from gas to physiological saline at 310 K: Linear free energy relationships [J].
Abraham, Michael H. ;
Ibrahim, Adam ;
Acree, William E., Jr. .
FLUID PHASE EQUILIBRIA, 2007, 251 (02) :93-109
[9]   Air to fat and blood to fat distribution of volatile organic compounds and drugs: Linear free energy analyses [J].
Abraham, Michael H. ;
Ibrahim, Adam .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2006, 41 (12) :1430-1438
[10]   A data base for partition of volatile organic compounds and drugs from blood/plasma/serum to brain, and an LFER analysis of the data [J].
Abraham, Michael H. ;
Ibrahim, Adam ;
Zhao, Yuan ;
Acree, William E., Jr. .
JOURNAL OF PHARMACEUTICAL SCIENCES, 2006, 95 (10) :2091-2100