title: Optimization of trans-Resveratrol bioavailability for human therapy.
abstract: We have developed an innovative soluble galenic form to overcome the low absorption of trans-Resveratrol (t-Res) as a dry powder. We present here data on pharmacokinetics, bioavailability, and toxicity of t-Res in human volunteers treated with this soluble form, plus additional data on biological effects in rodents. Fifteen healthy volunteers of both sexes received 40 mg of t-Res in two forms, the soluble formulation (caplets) and the original powder (capsules), in a crossover design. Blood samples were collected at 15 min, 30 min, and every hour for 5 h. Plasma concentrations of t-Res and its metabolites were analyzed by liquid chromatography and mass spectrometry. The single dose (40 mg) of the soluble t-Res was well absorbed and elicited biologically efficient blood levels (0.1-6 μM) for several hours, despite metabolization into glucuronide and sulfate conjugates coupled to renal elimination. In contrast, t-Res administered as a dry powder barely elicited efficient blood levels for a short duration. The new formulation led to 8.8-fold higher t-Res levels in plasma versus the powder. t-Res metabolism was not modified and neither intolerance nor toxicity were observed during the study and the following week. The soluble formulation elicited a robust anti-inflammatory effect in various tissues of mice fed a high-fat diet, while dry powder t-Res was almost inactive. Our data suggest that significant improvements in t-Res bioavailability and efficiency can be obtained by this soluble galenic form, also allowing lower doses. The use of t-Res in human therapy is thus greatly facilitated and the toxicity risk is reduced.
authors: University Aix Marseille, INRA UMR 1260, 13385 Marseille, France.
authors: Marie Josephe
authors: MJ
authors: Amiot
authors: Beatrice
authors: B
authors: Romier
authors: Thi-Mai Anh
authors: TM
authors: Dao
authors: Raphaelle
authors: R
authors: Fanciullino
authors: Joseph
authors: J
authors: Ciccolini
authors: Remy
authors: R
authors: Burcelin
authors: Laurent
authors: L
authors: Pechere
authors: Claude
authors: C
authors: Emond
authors: Jean-François
authors: JF
authors: Savouret
authors: Eric
authors: E
authors: Seree
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001682:Biological Availability; D002214:Capsules; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D011208:Powders; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D000975:Antioxidants; D002214:Capsules; D011208:Powders; D013267:Stilbenes; D000077185:Resveratrol