Review of theoretical passive drug absorption models: Historical background, recent developments and limitations

doi:10.1016/S0031-6865(96)00031-3

Pharmaceutica Acta Helvetiae

Volume 71, Issue 5, November 1996, Pages 309-327

Pharmaceutica Acta H...

https://doi.org/10.1016/S0031-6865(96)00031-3 Get rights and content

Abstract

In the drug discovery process the optimization of a promising lead to an orally bioavailable drug remains a difficult task. Recent progress in the understanding of the role of physicochemical properties in membrane permeability relevant to important processes such as drug absorption and blood-brain barrier crossing, brings rational drug delivery more within reach. In the last thirty years a number of theoretical transport and absorption models have been developed to describe mathematically how a drug is being passively transported from its site of administration to its site of action and how a compound passes a membrane. The goal of such models is to rationalize the physical significance of the observed non-linear structure-permeability relationships. The models are based on various views on the composition of the biological membranes and on the underlying diffusion and distribution mechanisms. Often simplifications reducing the mathematical complexity are made. We review here a selection of the most important models and discuss modern views on the role of lipophilicity and various pathways through membranes.

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ReviewReview of theoretical passive drug absorption models: Historical background, recent developments and limitations

Abstract

Biochem. Biophys. Res. Comm.

Chemom. Intell. Lab. Syst.

Clin. Gastroenterol.

J. Pharm. Sci.

J. Pharm. Sci.

Pharmac. Ther.

J. Pharm. Sci.

J. Pharm. Sci.

J. Pharm. Sci.

Int. J. Pharm.

Biophys. J.

J. Pharm. Sci.

J. Pharm. Sci.

J. Pharm. Sci.

J. Pharm. Sci.

J. Pharm. Sci.

The factors that influence skin penetration of solutes

J. Pharm. Pharmacol.

Cell culures as models for drug absorption across the intestinal mucosa

Crit. Rev. Ther. Drug Carrier Syst.

Assessment of distribution-pH profiles

The influence of alkylsubstitution in acids on their performance in the buccal absorption test

J. Pharm. Pharmacol.

Acidification in the rat proximal jejenum

J. Physiol.

Reaktionsgeschwindigkeit in heterogenen Systemen

Z. Phys. Chem.

A new method for estimating dermal absorption from chemical exposure: 2. Effect of molecular weight and octanol-water partitioning

Pharm. Res.

The influence of molecular volume and hydrogen-bonding on peptide transport across epithelial membranes

Pharm. Res.

The distribution of organic copounds between iso-octanol and water

Acta Chem. Scand.

The partition of organic compounds between higher alcohols and water

Acta Chem. Scand.

Physicochemical and biological factors that influence a drug's cellular permeability by passive diffusion

Rationally designed model with general applicability for absorption by passive diffusion

Development and application of model-based relationships describing ‘in vivo’ absorption kinetics

Polar intermolecular interactions encoded in partition coefficients: An indirect estimation of hydrogen-bonding parameters of polyfunctional solutes

J. Phys. Chem.

Mass transport phenomena and models: Theoretical concepts

J. Pharm. Sci.

A new substituent constant, π, derived from partition coefficients

J. Am. Chem. Soc.

Hydrogen-bonding parameter and its significance in quantitative structure-activity studies

J. Med. Chem.

A quantitative approach to biochemical structure-activity relationships

Accounts Chem. Res.

Quantitative structure-activity relationships in drug design

Rate-limiting barriers to intestinal drug absorption: A review

J. Pharmacokin. Biopharm.

Rate limiting steps and factors in drug absoption

Pharmakokinetik und Arzneimittelentwicklung

Deutsche Apotheker Z.

Caco-2 cell monolayers as a model for drug transport across the intestinal mucosa

Pharm. Res.

Oral delivery of 5-HT1D receptor agonists: Towards the discovery of 311C90, a novel anti-migraine agent

Headache

Physical model approach to the design of drugs with improved intestinal absorption

Advancing quantitative and mechanistic approaches in interfacing gastrointestinal drug absorption studies in animals and man

On the mechanism of intestinal absorption of drugs

J. Pharm. Exp. Ther.

A reevaluation of the importance of partition coefficients in the gastro-intestinal absorption of anutrients

J. Pharmacol. Exp. Ther.

Drug absorption limited by P-glycoprotein- mediated secretory drug transport in human intestinal epithelial Caco-2 cell layers

Pharm. Res.

A comparision of two related approaches to modelling in QSAR

Eur. J. Med. Chem.

Absorption and excretion of drugs. XXX. On the mechanisms of rectal absorption of sulfonamides

Chem. Pharm. Bull.

Absorption and excretion of drugs: XXX. Absorption of barbituric acid derivates from rat stomach

Chem. Pharm. Bull.

Absorption and excretion of drugs. XXXII. Absorption of barbituric acid derivates from rat small intestine

Chem. Pharm. Bull.

Review
Review of theoretical passive drug absorption models: Historical background, recent developments and limitations