From HODGKINE "-at-" prince.mm.wyeth.com Wed Jan 11 11:10:38 1995 Received: from mail1 for HODGKINE #at# prince.mm.wyeth.com by www.ccl.net (8.6.9/930601.1506) id KAA25834; Wed, 11 Jan 1995 10:00:12 -0500 Received: from mr.wyeth.com by mail1.wyeth.com (PMDF V4.2-14 #5660) id <01HLPL1ETVO00016IL \\at// mail1.wyeth.com>; Wed, 11 Jan 1995 06:22:47 EST Received: with PMDF-MR; Wed, 11 Jan 1995 06:18:49 EST MR-Received: by mta PRIN1; Relayed; Wed, 11 Jan 1995 06:18:49 -0500 MR-Received: by mta MAIL1; Relayed; Wed, 11 Jan 1995 06:21:54 -0500 Disclose-recipients: prohibited Date: Wed, 11 Jan 1995 11:28:22 -0500 (EST) From: "Hodgkin, Ed" Subject: Oral bioavailability To: "chemistry*- at -*ccl.net" Message-id: <01HLPL1FWGK60016IL "-at-" mr.wyeth.com> MIME-version: 1.0 Content-type: TEXT/PLAIN; CHARSET=US-ASCII Content-transfer-encoding: 7BIT UA-content-id: Oral bioavailability X400-MTS-identifier: [;94816011105991/366882#* at *#PRINCE] A1-type: MAIL Hop-count: 1 From: Hodgkin, Ed Date: Wed, Jan 11, 1995 11:28 AM Subject: Oral bioavailability To: chemistry[ AT ]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 -8 at 8- prince.mm.wyeth.com