From: Hodgkin, Ed
Date: Wed, Jan 11, 1995 11:28 AM
Subject: Oral bioavailability
To: chemistry -x- at -x- ccl.net
Reply to Andy Sheppard's question about prediction of oral bioavailability.
I suggest you look at the following references:
Taylor, Lynch and Leahy "Models for intestinal permeability to drugs"
Delivery to the Gastrointestinal Tract, pub. Ellis Horwood, 1989, page 147. -
this is a discussion of model systems for drug absorption using rat jejunum and
ileum as well as model solvent systems. Subsequent to this work, this group
(Zeneca) has tried QSAR approaches for prediction of absorption with
considerable success, although I don't think that is published in detail.
Hill et al, Headache (1994) 34: 308 "Oral delivery of 5HT1D receptor
- this is a short account of the Wellcome group's use of physical property
measurements (both experimental and calculated) to improve the bioavailability
of a series of compounds.
Conradi et al, Pharm. Res. (1991) 8: 1453 "Influence of Peptide Structure
Transport Across CACO-2 Cells" - discusses CACO-2 cells as a model for drug
absorption. Absorption seems to increase with removal of H-bond donors. Other
authors have reported the same.
I consider the 3 refs above to be "highlights". Some other papers of
Hirono et al, Biol Pharm Bull (1994) 17:306 - QSAR approach
Amidon and Lee, Annu Rev Pharmacol Toxicol (1994) 34:321 - Review of peptide
Paterson et al, QSAR (1994) 13:4 - Solvent system
Ranadive et al, Pharm Res (1994) 9:1480 - ACE inhibitors
Taylor et al, J Pharm Pharmacol (1985) 37:280 - Beta-blockers
Nook et al. J Pharmaceutics (1988) 43:119 - Relationship between partition
coefficients and absorption kinetics
Karls et al, Pharm Res (1991) 8:1477 - The importance of desolvation energy
Edward E. Hodgkin MA DPhil
Wyeth Research (UK) Limited
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