Predicting Drug Absorption: How Nature Made It a Difficult Problem
Significant recent work has focused on predicting drug absorption from structure. Several misperceptions regarding the nature of absorption seem to be common. Among these is that intestinal absorption, permeability, fraction absorbed, and, in some cases, even bioavailability, are equivalent properti...
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| Published in | The Journal of pharmacology and experimental therapeutics Vol. 303; no. 3; pp. 889 - 895 |
|---|---|
| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Society for Pharmacology and Experimental Therapeutics
01.12.2002
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Significant recent work has focused on predicting drug absorption from structure. Several misperceptions regarding the nature
of absorption seem to be common. Among these is that intestinal absorption, permeability, fraction absorbed, and, in some
cases, even bioavailability, are equivalent properties and can be used interchangeably. A second common misperception is that
absorption, permeability, etc. are discrete, fundamental properties of the molecule and can be predicted solely from some
structural representation of the drug. In reality, drug absorption is a complex process dependent upon drug properties such
as solubility and permeability, formulation factors, and physiological variables, including regional permeability differences,
pH, lumenal and mucosal enzymology, and intestinal motility, among others. This article will explore the influence of these
different variables on drug absorption and the implications with regards to attempting to develop predictive drug absorption
algorithms. |
|---|---|
| AbstractList | Significant recent work has focused on predicting drug absorption from structure. Several misperceptions regarding the nature of absorption seem to be common. Among these is that intestinal absorption, permeability, fraction absorbed, and, in some cases, even bioavailability, are equivalent properties and can be used interchangeably. A second common misperception is that absorption, permeability, etc. are discrete, fundamental properties of the molecule and can be predicted solely from some structural representation of the drug. In reality, drug absorption is a complex process dependent upon drug properties such as solubility and permeability, formulation factors, and physiological variables, including regional permeability differences, pH, lumenal and mucosal enzymology, and intestinal motility, among others. This article will explore the influence of these different variables on drug absorption and the implications with regards to attempting to develop predictive drug absorption algorithms. Significant recent work has focused on predicting drug absorption from structure. Several misperceptions regarding the nature of absorption seem to be common. Among these is that intestinal absorption, permeability, fraction absorbed, and, in some cases, even bioavailability, are equivalent properties and can be used interchangeably. A second common misperception is that absorption, permeability, etc. are discrete, fundamental properties of the molecule and can be predicted solely from some structural representation of the drug. In reality, drug absorption is a complex process dependent upon drug properties such as solubility and permeability, formulation factors, and physiological variables, including regional permeability differences, pH, lumenal and mucosal enzymology, and intestinal motility, among others. This article will explore the influence of these different variables on drug absorption and the implications with regards to attempting to develop predictive drug absorption algorithms. |
| Author | Philip S. Burton Benny M. Amore Thomas J. Vidmar Jay T. Goodwin |
| Author_xml | – sequence: 1 givenname: Philip S surname: Burton fullname: Burton, Philip S email: philip.s.burton@pharmacia.com organization: Drug Absorption and Transport, Pharmacia, Kalamazoo, Michigan 49007, USA. philip.s.burton@pharmacia.com – sequence: 2 givenname: Jay T surname: Goodwin fullname: Goodwin, Jay T – sequence: 3 givenname: Thomas J surname: Vidmar fullname: Vidmar, Thomas J – sequence: 4 givenname: Benny M surname: Amore fullname: Amore, Benny M |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/12438506$$D View this record in MEDLINE/PubMed |
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| References_xml | – ident: 2019081412094464000_303.3.889.3 doi: 10.1093/jac/13.5.465 – ident: 2019081412094464000_303.3.889.11 doi: 10.1021/jm000292e – ident: 2019081412094464000_303.3.889.14 doi: 10.1021/jm980527a – ident: 2019081412094464000_303.3.889.44 doi: 10.1021/ci980029a – ident: 2019081412094464000_303.3.889.45 doi: 10.1172/JCI107810 – ident: 2019081412094464000_303.3.889.17 – volume: 20 start-page: 10 year: 1977 ident: 2019081412094464000_303.3.889.10 article-title: The epithelial junction: Bridge, gate and fence. publication-title: Physiologist contributor: fullname: Diamond – ident: 2019081412094464000_303.3.889.7 doi: 10.1016/S0031-6865(96)00031-3 – ident: 2019081412094464000_303.3.889.46 doi: 10.1146/annurev.pharmtox.40.1.133 – ident: 2019081412094464000_303.3.889.32 doi: 10.1046/j.1432-1327.1998.2510252.x – ident: 2019081412094464000_303.3.889.37 doi: 10.1016/S0169-409X(02)00006-6 – ident: 2019081412094464000_303.3.889.2 doi: 10.1002/jps.2600841011 – ident: 2019081412094464000_303.3.889.49 – ident: 2019081412094464000_303.3.889.38 doi: 10.1016/0005-2736(95)00030-7 – ident: 2019081412094464000_303.3.889.35 doi: 10.1021/jm001101a – ident: 2019081412094464000_303.3.889.19 doi: 10.1016/S0169-409X(00)00130-7 – ident: 2019081412094464000_303.3.889.20 – ident: 2019081412094464000_303.3.889.18 – volume: 10 start-page: 1027 year: 1993 ident: 2019081412094464000_303.3.889.22 article-title: Effect of sodium acid pyrophosphate on ranitidine bioavailability and gastrointestinal transit time. publication-title: Pharm Res (NY) doi: 10.1023/A:1018918907670 contributor: fullname: Koch – volume: 9 start-page: 1 year: 1985 ident: 2019081412094464000_303.3.889.30 article-title: First-pass elimination. 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of absorption seem to be common.... Significant recent work has focused on predicting drug absorption from structure. Several misperceptions regarding the nature of absorption seem to be common.... |
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| SubjectTerms | Administration, Oral Animals Dose-Response Relationship, Drug Forecasting Humans Intestinal Absorption - physiology Permeability Pharmaceutical Preparations - metabolism Structure-Activity Relationship |
| Title | Predicting Drug Absorption: How Nature Made It a Difficult Problem |
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