Subject: Oral availability of drugs...

From: [email-masked]
Date: Tue, 10 Jan 95 13:45:01 GMT

Dear Readers,

I would be grateful for comments, ideas, anecdotes, references etc. on the
following topic:

In the area of drug research, a frequent problem which arises is that of
obtaining oral-availability: it is usually more desirable to have an orally
active compound than one which is active only when injected.

What I want to know is the following:

1  Is it possible to predict whether a compound will be orally active?

2  On observing a compound has little or no oral activity, are there any
   structural modifications which can be used to increase the oral activity
   of the compound?

3  Is it possible to use an adjuvant to increase the absorption of a
   weakly orally active compound?

4  Are there any in vitro test systems which will predict whether a
   compound is orally active? If there are such test systems, are they
   available commercially or have they been devloped in-house?

I will summarise useful information to the net.

Andy Sheppard
Ferring Research Institute
[email-masked]

[crossposted to newsgroups bionet.general, bionet.molbio.methds-reagnts,
 bionet.molec-model and the Computational Chemistry list]

---

From: Stefan Unger <[email-masked]>
Date: Tue, 10 Jan 1995 08:38:51 -0800 (PST)

> 1  Is it possible to predict whether a compound will be orally active?
Oral activity is dependent upon many factors: dosage formulation and 
route (pill, gavage, liquid ...), inherent solubility, microcrystalline 
state, species, metabolism, etc. 
>    structural modifications which can be used to increase the oral activity
It would depend on the reason for lack of activity.  See 4.  You could 
try to block metabolic deactivation, improve solubility, improve 
formulation, etc.
>    weakly orally active compound?
Yes, liposome formulation, for example.  Various microcrystalline forms 
may have different solubilities, etc.
>    available commercially or have they been devloped in-house?
You can get software to predict solubility and lipophilicity, and also 
metabolism.  Empirically, most CNS active agents (and most "typical" 
drugs) seem to have an octanol/aqueous partition coefficient of logP = 2 
(approx).  But this depends upon class, e.g. penicillins are much more 
hydrophilic.  A good strategy might be to try to approximate the phys-chem
properties of known structurally related orally active compounds 
(solubility and log P (oct).
Hope this helps.  Contact me off-line for informaiton on software.  
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