Clinical pharmacokinetics of kavalactones after oral dosing of standardized kava extract in healthy volunteers.
Clinical pharmacokinetics of kavalactones after oral dosing of standardized kava extract in healthy volunteers.
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DOI：
10.1016/j.jep.2022.115514
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发表时间：
2022-10-28
影响因子：
5.4
通讯作者：
Sharma, Abhisheak
中科院分区：
文献类型：
--
作者：
Kanumuri, Siva Rama Raju;Mamallapalli, Jessica;Nelson, Robyn;McCurdy, Christopher R.;Mathews, Carol A.;Xing, Chengguo;Sharma, Abhisheak
卡瓦胡椒福斯特（菊科），通常称为卡瓦，由于其放松的特性，几个世纪以来一直被用作传统饮料。卡瓦内酯被认为是卡瓦的有益作用的主要成分。尽管卡瓦广泛使用，但文献中没有临床药代动力学数据;因此，本研究的结果对于卡瓦未来临床评价的剂量计算至关重要。本研究的目的是检查健康志愿者使用两种剂量方案口服不含黄素卡瓦蛋白A/B的标准化卡瓦提取物胶囊后六种主要卡瓦内酯的临床药代动力学。开发并验证了一种灵敏、可靠和特异的超高压液相色谱-质谱（UPLC-MS/MS）方法，用于同时定量人血浆中6种主要的麻醉椒内酯（麻醉椒素、二氢麻醉椒素、麻醉椒苦素、二氢麻醉椒苦素、羊果苷和去甲氧基羊果苷）和2种黄素麻醉椒素（A和B）。在10名健康志愿者口服标准化卡瓦产品后评估药代动力学特征，并使用经验证的UPLC-MS/MS方法分析血浆样品中的6种卡瓦内酯和2种黄素卡瓦菌素。对浓度-时间数据进行药代动力学分析。发现麻醉椒内酯的全身暴露按以下顺序：二氢醉椒素>二氢麻醉椒苦素>醉椒素>麻醉椒苦素>羊果苷。去甲氧基麻醉椒素仅在几个时间点可定量，而黄素醉椒素A和黄素醉椒素B不存在于任何血浆样品中。观察到5种麻醉椒内酯随时间快速吸收，1 - 3 h达到最大血药浓度。在75 - 225 mg麻醉椒内酯剂量范围内，确立了药代动力学的剂量比例性。在多次给药研究中，观察到食入后卡法根内酯的吸收程度显著降低。在健康志愿者中进行了卡瓦的单次和多次给药临床药代动力学研究，单次给药（225 mg）后观察到更高的卡瓦内酯暴露量，而每天三次（3 × 75 mg）给药后观察到更长的暴露持续时间。
Piper methysticum G. Forst. (Piperaceae), commonly known as kava, has been used as a traditional beverage for centuries for its relaxing properties. Kavalactones are considered to be the major constituents responsible for kava’s beneficial effects. Despite the extensive use of kava, clinical pharmacokinetic data is not available in the literature; therefore, the findings of this study will be critical for the dosage calculations for future clinical evaluation of kava. The aim of the current study is to examine the clinical pharmacokinetics of six major kavalactones following oral dosing of flavokavain A/B-free standardized kava extract capsules in healthy volunteers using two dosage regimens. A sensitive, reliable, and specific ultra-high pressure liquid chromatography-mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous quantification of six major kavalactones (kavain, dihydrokavain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin) and two flavokavains (A and B) in human plasma. Pharmacokinetic profiles were assessed in ten healthy volunteers after oral doses of standardized kava product, and plasma samples were analyzed for six kavalactones and two flavokavains using the validated UPLC-MS/MS method. Concentration-time data was subjected to pharmacokinetic analysis. The systemic exposure of the kavalactones was found to be in the following order: dihydrokavain > dihydromethysticin > kavain > methysticin > yangonin. Desmethoxyyangonin was quantifiable only at a couple of time points, while flavokavain A and flavokavain B were not present in any of the plasma samples. Fast absorption of five kavalactones was observed with time to reach the maximum plasma concentration of 1–3 h. A dose proportionality in pharmacokinetics was established from 75 to 225 mg of kavalactone doses. In the multiple-dose study, a significant reduction in the extent of absorption of kavalactones with food was observed. Single and multiple-dose clinical pharmacokinetic studies for kava were performed in healthy volunteers, and higher exposure to the kavalactones was observed after single-dosing (225 mg), while a longer duration of exposure was observed after three times a day (3 × 75 mg) dosing.
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影响因子：
2.7
作者：
Mamallapalli, Jessica;Kanumuri, Siva Rama Raju;Xing, Chengguo
通讯作者：
Xing, Chengguo
影响因子：
7.9
作者：
Einbond, L. S.;Negrin, A.;Balick, M. J.
通讯作者：
Balick, M. J.
影响因子：
3.7
作者：
Li X;Liu Z;Xu X;Blair CA;Sun Z;Xie J;Lilly MB;Zi X
通讯作者：
Zi X
DOI：
10.1158/1940-6207.capr-13-0301
发表时间：
2014-01
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Leitzman P;Narayanapillai SC;Balbo S;Zhou B;Upadhyaya P;Shaik AA;O'Sullivan MG;Hecht SS;Lu J;Xing C
通讯作者：
Xing C
影响因子：
4.1
作者：
Narayanapillai SC;Leitzman P;O'Sullivan MG;Xing C
通讯作者：
Xing C