Pharmacokinetics of 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol and conjugate metabolites in healthy human subjects.
Pharmacokinetics of 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol and conjugate metabolites in healthy human subjects.
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DOI：
10.1158/1055-9965.epi-07-2934
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发表时间：
2008-08
期刊：
影响因子：
--
通讯作者：
Brenner DE
中科院分区：
文献类型：
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作者：
Zick SM;Djuric Z;Ruffin MT;Litzinger AJ;Normolle DP;Alrawi S;Feng MR;Brenner DE
生姜显示出有前途的抗癌特性。没有研究检查生姜成分6-，8-，10-姜辣素和6-姜烯酚在人体内的药代动力学。我们用6-、8-、10-姜辣素和6-姜烯酚进行了一项临床试验，检查这些分析物及其缀合代谢物的药代动力学和耐受性。人类志愿者以100 mg至2.0 g的剂量给予生姜（N=27），并在单次口服剂量后15分钟至72小时获得血液样品。参与者以剂量递增的方式分配，从100 mg开始。除1.0 g（N=6）和2.0 g（N=9）外，每个剂量组共有3名受试者。没有参与者检测到游离的6-，8-，10-姜辣素或6-姜烯酚，但检测到6-，8-，10-姜辣素和6-姜烯酚葡萄糖苷酸。在1.0 g剂量以上检测到6-姜辣素硫酸盐缀合物，但除了一名参与者可检测到8-姜辣素硫酸盐外，没有可检测到10-姜辣素或6-姜烯酚硫酸盐。2.0 g剂量的Cmax和AUC值（平均值±SE）估计值为0.85±0.43、0.23±0.16、0.53±0.40和0.15±0.12 μg/mL ; 6-、8-、10-姜辣素和6-姜烯酚的Cmax和AUC值估计值为65.6.33±44.4、18.1±20.3、50.1±49.3和10.9±13.0 μg·hr/mL。相应的tmax值分别为65.6±44.4、73.1±29.4、75.0±27.8和65.6±22.6分钟，分析物的消除半衰期<2小时。8-、10-姜辣素和6-姜烯酚缀合物以葡糖苷酸或硫酸盐缀合物的形式存在，而不是以混合缀合物的形式存在，尽管6-、10-姜辣素是例外。6-、8-、10-姜辣素和6-姜烯酚在口服给药后被吸收，并可作为葡糖苷酸和硫酸盐结合物被检测到。
Ginger demonstrates promising anticancer properties. No research has examined the pharmacokinetics of the ginger constituents 6-, 8-, 10-gingerol and 6-shogaol in humans. We conducted a clinical trial with 6-, 8-, 10-gingerol and 6-shogaol examining the pharmacokinetics and tolerability of these analytes and their conjugate metabolites Human volunteers were given ginger at doses from 100 mg, to 2.0 g (N=27), and blood samples were obtained at 15 minutes to 72 hours after a single oral dose. Participants were allocated in a dose-escalation manner starting with 100 mg. There was a total of three participants at each dose except for 1.0 g (N=6) and 2.0 g (N=9). No participant had detectable free 6-, 8-, 10-gingerol or 6-shogaol, but 6-, 8-, 10-gingerol and 6-shogaol glucuronides were detected. The 6-gingerol sulfate conjugate was detected above the 1.0 g dose but there were no detectable 10-gingerol or 6-shogaol sulfates except for one participant with detectable 8-gingerol sulfate. The Cmax and AUC values (Mean±SE) estimated for the 2.0 g dose are 0.85±0.43, 0.23±0.16, 0.53±0.40, and 0.15±0.12 μg/mL ; and 65.6.33±44.4, 18.1±20.3, 50.1±49.3, and 10.9±13.0 μg·hr/mL for 6-, 8-, 10-gingerol, and 6-shogaol. The corresponding tmax values are 65.6±44.4, 73.1±29.4, 75.0±27.8, and 65.6±22.6 minutes and the analytes had elimination half-lives < 2hr. The 8-, 10-gingerol and 6-shogaol conjugates were present as either glucuronide or sulfate conjugates, not as mixed conjugates, although 6-, 10-gingerol were an exception. Six-, 8-, 10-gingerol and 6-shogaol is absorbed after oral dosing and can be detected as glucuronide and sulfate conjugates.