Oral bioavailability



 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"
 in Drug
 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
 agonists"
 - 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
 on
 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
 potential
 interest are:
 Hirono et al, Biol Pharm Bull (1994) 17:306 - QSAR approach
 Amidon and Lee, Annu Rev Pharmacol Toxicol (1994) 34:321 - Review of peptide
 absorption
 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
 Huntercombe Lane South
 Taplow, Maidenhead
 Berks SL6 0PH
 United Kingdom
 Tel: +44 628 414887
 Fax: +44 628 414825
 E-mail: hodgkine -x- at -x- prince.mm.wyeth.com