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New Resveratrol PK study in humans w/ multiple dosing regime


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#1 malbecman

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Posted 09 February 2009 - 04:55 PM


I have not had time to read and digest this (pun intended) but it looks interesting and apparently confirms many of the earlier findings, eg, low bioavailability, high interindividual variability, etc.

Mol Nutr Food Res. 2009 Feb 4. [Epub ahead of print]
Pharmacokinetic and safety profile of trans-resveratrol in a rising multiple-dose study in healthy volunteers.
Almeida L, Vaz-da-Silva M, Falcão A, Soares E, Costa R, Loureiro AI, Fernandes-Lopes C, Rocha JF, Nunes T, Wright L, Soares-da-Silva P.
Department of Research and Development, BIAL - Portela & Co SA, S Mamede do Coronado, Portugal. Fax: +351-22-9866192.

This was a double-blind, randomised, placebo-controlled study to investigate the pharmacokinetics and safety of trans-resveratrol. In four groups of ten healthy adult subjects (five males and five females), two subjects were randomized to receive placebo and eight subjects to receive trans-resveratrol 25, 50, 100 or 150 mg, six times/day, for thirteen doses. Peak plasma concentrations of trans-resveratrol were reached at 0.8-1.5 h postdose. Following the 13th dose of trans-resveratrol 25, 50, 100 and 150 mg, mean peak plasma concentration (C(max)) was 3.89, 7.39, 23.1 and 63.8 ng/mL and mean area under the plasma concentration-time curve (AUC(0-tau)) was 3.1, 11.2, 33.0 and 78.9 ng.h/mL. Interindividual variability was high, with coefficients of variation >40%. Trans-resveratrol half-life was 1-3 h following single-doses and 2-5 h following repeated dosing. Trough (C(min)) concentrations were less, not double equals1 ng/mL following 25 and 50 mg, 3 ng/mL following 100 mg and < 10 ng/mL following 150 mg. Trans-resveratrol pharmacokinetics showed circadian variation. Adverse events were mild in severity and similar between all groups. In conclusion, repeated administration was well-tolerated but produced relatively low plasma concentrations of trans-resveratrol, despite the high doses and short dosing interval used. Bioavailability was higher after morning administration.

PMID: 19194969

#2 FunkOdyssey

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Posted 09 February 2009 - 05:01 PM

I have not had time to read and digest this (pun intended) but it looks interesting and apparently confirms many of the earlier findings, eg, low bioavailability, high interindividual variability, etc.

Mol Nutr Food Res. 2009 Feb 4. [Epub ahead of print]
Pharmacokinetic and safety profile of trans-resveratrol in a rising multiple-dose study in healthy volunteers.
Almeida L, Vaz-da-Silva M, Falcão A, Soares E, Costa R, Loureiro AI, Fernandes-Lopes C, Rocha JF, Nunes T, Wright L, Soares-da-Silva P.
Department of Research and Development, BIAL - Portela & Co SA, S Mamede do Coronado, Portugal. Fax: +351-22-9866192.

PMID: 19194969


What were the adverse effects?

Edited by Michael, 10 February 2009 - 12:31 AM.


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#3 JLL

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Posted 09 February 2009 - 07:24 PM

Headache
Dysmenorrhea
Nasopharyngitis
Dyspepsia
Precordial pain
Lower urinary tract infection
Creatine phosphokinase increased
Dorsal pain
Epididymitis
Myalgia of lower extremities
Dizziness
Somnolence

Only headache was reported by more than one subject.

#4 drmz

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Posted 10 February 2009 - 08:49 AM

finally some human data.....hopefully we get some more data in the future about resveratrol in humans regarding bioavailability.

#5 geddarkstorm

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Posted 10 February 2009 - 04:32 PM

The thing with resveratrol, and which I'd really wish would be studied, is that some proportion of the glucuronidated form is actually countable as aglycone resveratrol. That is, even though the serum levels of aglycone resveratrol are low and seem to imply bioavailability is also low, using radioactive resveratrol in rats has shown this to not be the case. The glucuronidated resveratrol is deglycosylated upon cellular uptake, so that in the living cell, resveratrol is in its natural form preferentially, and is retained as such. That is what ultimately determines bioavailability - how much resveratrol is aglycone in the living cell, not serum.

Now, we don't know if this happens in humans, or especially to what extent, but considering all we've seen, it's highly likely (or it could be only a very low amount of resveratrol is necessary to kickstart Nampt and get the whole system going, or both). That being the case, the actual bioavailability of resveratrol is [aglycon]*([glucuronidated]*percentage of conversion).

This may or may not apply to the sulfonated form, but again, aglycone resveratrol is the type retained in rat tissues over both the sulfonated and glucuonidated forms - though apparently in rats glucuronidation is predominant while in humans it appears to be sulfation.

Edited by geddarkstorm, 10 February 2009 - 04:33 PM.


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#6 Crepulance

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Posted 12 February 2009 - 10:37 AM

I don't know how to interpret those readings, or what to make of them I should say in terms of perspective. Is that good bioavailability or not? Which doses had the better availability?


Crep




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