Here is a little data i took from a patent SOMEBODY NEEDS TO ALLOW HTML CODE IN THIS SUB-FORUM.
http://www.baresvera...rmULations_RES/
As mentioned above, certain compositions of matter of the invention comprise
an aqueous preparation of preferably substituted amorphous cyclodextrin and
one or more sirtuin modulators. The relative amounts of sirtuin modulators and
cyclodextrin will vary depending upon the relative amount of each of the sirtuin
modulators and the effect of the cyclodextrin on the compound. In general, the
ratio of the weight of compound of the sirtuin modulators to the weight of cyclodextrin
compound will be in a range between 1:1 and 1:100. A weight to weight ratio
in a range of 1:5 to 1:50 and more preferably in a range of 1:10 to 1:20 of
the compound selected from sirtuin modulators to <strong>cyclodextrin are believed
to be the most effective for increased circulating availability of the sirtuin
modulator.
150 mM SRT501 = 150mM resveratrol.
FIG. 23 shows a comparison of the plasma profile from unprocessed resveratrol
in methylcellulose (MC) (Res; mean particle size approx. 13 um) to micronized
resveratrol (Micro; mean particle size approx. 1.0 um) in either methylcellulose
(MC) or HPMC/DOSS after oral gavage in mice at the doses shown.
FIG. 24 shows a comparison of the plasma profile from micronized resveratrol
(Micro; mean particle size approx. 1.0 um) in ether Tween 80 or HPMC/DOSS
after oral gavage in mice at the doses shown.</td>
FIG. 25 shows a comparison of the plasma profile from micronized resveratrol
in HPMC/DOSS following either oral gavage or intraperitoneal injection in
mice at the doses shown.</td>
FIG. 26 shows a comparison of various formulations of resveratrol in rats
following intraperitoneal administration at the indicated doses.</td>
FIG. 27 shows a comparison of various formulations of resveratrol in rats
following oral administration at the indicated doses. </td>
TABLE II Comparison of pharmacokinetic parameters for IP dosing of various resveratrol formulations in rats.
DMSO solution Captisol solution Unprocessed in IP Comparison (200 mg/kg) (50 mg/kg) MC (50 mg/kg)
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As can be seen, various dosing routes and/or formulations can be used to drive different PK parameters. For instance, with IP dosing, the captisol formulated resveratrol solution achieves a greater Cmax and AUC than the unprocessed resveratrol suspension. The DMSO resveratrol solution gives an intermediate Cmax and AUC. However, the resveratrol suspension showed the longest duration of detectable drug in the plasma as measured by T 1/2 . With oral dosing, the captisol solution again gave a higher Cmax as compared to oral dosing of the unprocessed resveratrol suspension. However, the resveratrol suspension gave a higher overall AUC and duration of detectable drug in the plasma. Based on these results, resveratrol can be formulated in different ways or delivered by different routes to either maximize absolute plasma levels (Cmax) or duration of exposure (AUC or T 1/2 ).
Edited by Hedgehog, 22 April 2008 - 07:57 PM.
