PharmPK Discussion - Bioavailability food effect and man vs animal

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On 21 Jun 2004 at 13:57:09, "Zutshi, Anup [USCRE/1017]" (anup.zutshi.-a-.pharmacia.com) sent the message

Dear PharmPK Listserve members
Does anybody know of literature references, text book citations or
anecdotal
information of the correlation of a food effect observed in animal
bioavailability studies with the same in humans. In other words, can the
effect of food on the bioavailability of a drug be predicted from
similar
animal studies. Please note that I am not concerned with the accuracy
of the
prediction--just that it can or cannot predict.
Thanks
Anup Zutshi

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On 22 Jun 2004 at 08:47:20, "Bales, Frank" (Frank.Bales.-at-.parexel.com) sent the message

Anup,
The predictability of the food effect may depend upon the nature of the
active. If the active is a hydrotrope, then there is likely poor
predictability.
Hydrotropes are molecules that have both non-polar (ring) structures
and polar ones. They self-associate in water in a way that is different
from surfactants: hydrotropic self-associations occur at higher
concentrations than do surfactant self-associations, and the
hydrotropic self-associations are able to solubilize greater amounts of
material. More importantly here, hydrotropes are used in combination
with surfactants for industrial and cosmetic purposes, and the
combinations have been shown to form "worm" and "branched" mixed
micelles, (Hassan, P.A.; Raghavan, S. R.; Kales, E.W.; Langmuir 2002,
18, 2543-2548). These can be of extended length, and can grow as long
as several microns, with radii of typically 2-3 nm (Clausen, T. M.;
Vinson, P. K.; Minter, J. R.; Davis, H. T.; Talmon, Y.; Miller, W. G.
J. Phys. Chem. 1992, 96, 474). It seems possible that actives that are
hydrotropes can be incorporated into mixed micelles in the presence of
bile salts and lecithin. The release of hydrotropes out of such mixed
micelles could be unpredictable.
  As a possible example of the (human) variability, consider the
published Important Warnings and Prescribing Information for Cordarone\0xC6
(Amiodarone HCl ). For example: "Food increases the rate and extent of
absorption of Cordarone. ... The area under the plasma
concentration-time curve (AUC) and the peak plasma concentration (Cmax)
of Amiodarone increased by 2.3 (range 1.7 to 3.6) and 3.8 (range 2.7 to
4.4) times, respectively, in the presence of food. Food also increased
the rate of absorption of Amiodarone".
  Regards,
Frank
Frank Bales, Ph.D.
  Senior Regulatory Consultant
  Worldwide Regulatory Affairs
  PAREXEL Intl.
  2520 Meridian Pkwy, Suite 200
  Durham, NC 27713
  (919) 294-5297 Phone
  Email: frankbales.-at-.msn.com
  frank.bales.aaa.parexel.com

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