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食物对反式白藜芦醇药代动力学特征的影响。

Effect of food on the pharmacokinetic profile of trans-resveratrol.

作者信息

Vaz-da-Silva M, Loureiro A I, Falcao A, Nunes T, Rocha J-F, Fernandes-Lopes C, Soares E, Wright L, Almeida L, Soares-da-Silva P

机构信息

Department of Research and Development, BIAL, S. Mamede do Coronado, Portugal.

出版信息

Int J Clin Pharmacol Ther. 2008 Nov;46(11):564-70. doi: 10.5414/cpp46564.

Abstract

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.

摘要

目的

据推测,反式白藜芦醇可能具有抗氧化、心脏保护、神经保护和癌症化学预防作用。本研究的目的是调查食物对口服反式白藜芦醇生物利用度的影响。

材料与方法

对24名健康受试者进行单中心、开放标签、随机、双向交叉研究。该研究包括两个连续的治疗期,中间有7天或更长时间的洗脱期。在每个研究期,受试者在标准高脂肪餐或禁食8小时后服用400毫克单剂量的反式白藜芦醇。

结果

反式白藜芦醇药代动力学参数存在较大的个体间差异。进食条件下平均±标准差最大血浆浓度(Cmax)为42.2±36.6纳克/毫升,禁食条件下为47.3±30.0纳克/毫升。达到Cmax的中位时间(tmax)进食时为2.0小时,禁食时为0.5小时(p<0.0001)。进食/禁食几何平均比值(GMR)和90%置信区间(90%CI),Cmax分别为79.4和53.8,117.0%;血浆浓度-时间曲线下面积(AUC0-∞)分别为106.0和86.8,128.0%。AUC0-∞和Cmax的GMR的90%CI超出了通常的生物等效性接受范围80%,125%,但AUC0-∞的接近生物等效性标准。

结论

口服400毫克单剂量反式白藜芦醇后,食物的存在显著延迟了吸收速率,这由Cmax和tmax反映。然而,由AUC-∞反映的吸收程度没有受到相关影响。

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