International Journal of Clinical Pharmacology and Therapeutics · 2008 · 101 citations · 13 references
PharmacyPharmacokineticsPharmacologyBioavailabilityClinical PharmacologyHuman NutritionDrug DispositionFood Effects On BioavailabilityFood Effects On Oral AbsorptionFood-effect StudiesArea Under The Plasma Concentration-time CurveGeometric Mean RatioHigh-calorie Meal EffectsHigh-fat Meal EffectsHigh-fat Meal StudyPharmacokinetic ParametersPlasma Concentration - Time ProfilePlasma Concentration-time Analysis
OBJECTIVE: It has been postulated that trans-resveratrol may act as an antioxidant, cardioprotective, neuroprotective and cancer chemopreventive agent. The objective of this study was to investigate the effect of food on the bioavailability of trans-resveratrol following oral administration. MATERIAL AND METHODS: Single-centre, open-label, randomized, 2-way crossover study on 24 healthy subjects. The study consisted of two consecutive treatment periods separated by a washout of 7 days or more. On each of the study periods subjects were administered a single-dose of 400 mg of trans-resveratrol following either a standard high fat content meal or 8 hs of fasting. RESULTS: There was a large interindividual variability in the trans-resveratrol pharmacokinetic parameters. Mean +/- SD maximum plasma concentration (Cmax) was 42.2 +/- 36.6 ng/ml in fed and 47.3 +/- 30.0 ng/ml in fasting conditions. Median time to Cmax (tmax) was 2.0 h in fed and 0.5 h in fasting (p < 0.0001). The fed/fasting geometric mean ratio (GMR) and 90% confidence interval (90% CI) were 79.4 and 53.8, 117.0% for Cmax, and 106.0 and 86.8, 128.0% for the area under the plasma concentration-time curve (AUC0- yen). The 90% CI for the GMR of AUC0- yen and Cmax fall outside the usual bioequivalence acceptance range of 80, 125%, but that of AUC0- yen was close to the bioequivalence standard. CONCLUSION: The rate of absorption of trans-resveratrol following an oral 400 mg single-dose was significantly delayed by the presence of food, as reflected by Cmax and tmax. However, the extent of absorption, as reflected by AUC- yen, was not affected in a relevant way.
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HIGH ABSORPTION BUT VERY LOW BIOAVAILABILITY OF ORAL RESVERATROL IN HUMANS
Thomas Walle, Faye Hsieh, Mark H. DeLegge et al. · Drug Metabolism and Disposition · 2004 · 1.8K citations