Dissolution and Pharmacokinetic of Ginsenosides Released From Cyclodextrin Based Chewable Tablets: a Comparative, Randomized, Crossover, Open-label Study in Healthy Human Subjects.
试验速览
- 阶段
- 1 期
- 状态
- 暂停
- 发起方
- 入组人数
- 3
- 试验地点
- 5
- 主要终点
- The area under the plasma concentration versus time curve (AUC, expressed in ng x h/mL) of Rk1.
研究概览
简要总结
This study will evaluate the relative bioavailability of ginsenosides Rg5, Rk1, and Ck of Red ginseng HRG80 preparations containing gamma-cyclodextrin (GCD) in the blood plasma of healthy subjects after oral administration of two different formulations of HRG80:
A. Capsules containing red ginseng preparation HRG80 (reference product) B. Chewable tablets containing red ginseng preparation HRG80 and GCD (modified product).
Dissolution testing measures the rate and extend water solubility of ginsenosides from the reference (A) and the modified (B) products. The difference of in vitro dissolution profiles between the reference (A) and modified (B) products will be assessed.
详细描述
A growing body of evidence suggests that gamma-cyclodextrin (GCD) can increase the clinical efficacy of water-insoluble biologically active compounds, which have low bioavailability. GCD is the most bio adaptable and applicable to increase the absorption of many drugs, including ginsenosides of Panax ginseng, by forming inclusion complexes or the form of GCD/drug conjugates. Ginsenosides have absolute bioavailability in the range from 0.2% to 48%, depending on the chemical structure and water solubility.
Hypothesis: gamma-cyclodextrin increases absorption and bioavailability of active constituents - Ginsenosides Rg5, Rk1, and Compound K (CK). The study aims to provide experimental evidence supporting or rejecting this hypothesis.
Sixteen healthy volunteers will be randomly assigned to receive two formulations, A and B, in two consecutive phases (Phase 1 and Phase) of an open-label study with a crossover design.
All patients will provide blood samples in each phase in each phase in 0.5, 0.75, 1, 2, 4, 6, 12, 24, and 48 hours (9 points) after drug administration, following will be a washout period for two weeks.
Subjects will be fasting for 10.00 hours before administering the investigational product. They will remain in the clinic post-dose until at least 24.00 hours each period, provided they are not suffering from any adverse event.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy volunteers, as determined by medical history, physical examination, and clinical laboratory testing,
- •Willingness to stay in the unit overnight for the duration of the study,
- •Provide a signed written informed consent.
排除标准
- •overweight (BMI >35 kg/m2),
- •pregnancy,
- •lactation,
- •drug abuse,
- •use of dietary supplements or any form of medication (with the exception of oral contraceptives),
- •heavy smokers, or ex-smokers with a remote history (> one pack/day),
- •frequent alcohol consumption (>20 g ethanol/d),
- •adherence to a restrictive dietary regimen,
- •physical activity of more than 5 h/wk,
- •respiratory tract infections, or suspicion thereof in the last 14 days before dosing,
- •history or presence of disease in the kidneys and heart, lungs, liver, the gastrointestinal tract, endocrine organs, or other conditions such as the metabolic disease is known to interfere with the absorption, distribution, metabolism, and excretion of drugs,
- •malignancy,
- •autoimmune disorders such as (but not limited to) lupus erythematosus, multiple sclerosis, rheumatoid arthritis, or sarcoidosis,
- •any other disease or condition, which, in the opinion of the Investigator, would make the subject unsuitable for this study,
- •currently taking medications known to be CYP2C9 inducers (i.e., carbamazepine and rifampicin).
结局指标
主要结局
The area under the plasma concentration versus time curve (AUC, expressed in ng x h/mL) of Rk1.
时间窗: 0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
The changes from the baseline the concentration (ng/ml) of Rk1 in blood plasma obtained after oral administration of the experimental product A or the active comparator B.
The area under the plasma concentration versus time curve (AUC, expressed in ng x h/mL) of ginsenoside Ck
时间窗: 0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
The changes from the baseline the concentration (ng/ml) of ginsenoside Ck in blood plasma obtained after oral administration of the experimental product A or the active comparator B.
The area under the plasma concentration versus time curve (AUC, expressed in ng x h/mL) of Rg5.
时间窗: 0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
The changes from the baseline the concentration (ng/ml) of Rg5 in blood plasma obtained after oral administration of the experimental product A or the active comparator B.
次要结局
- The absorption rate constant (Ka, h-1) of Rg5(0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose)
- The absorption rate constant (Ka, h-1) of Rk1(0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose)
- Maximum plasma concentration (Cmax, ng/ml), of Rk1(0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose)
- Time to reach maximum plasma concentration, Tmax (h) of Rg5 .(0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose)
- Maximum plasma concentration (Cmax, ng/ml), of Rg5(0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose)
- Time to reach maximum plasma concentration, Tmax (h) of Rk1(0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose)
- The absorption rate constant (Ka, h-1) of Ck(0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose)
- Time to reach maximum plasma concentration, Tmax (h) of Ck.(0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose)
- Maximum plasma concentration (Cmax, ng/ml), of Ck(0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose)
- Mean absorption time MAT (h) of Rg5(0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose)
- Mean absorption time MAT (h) of Rk1(0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose)
- Mean absorption time MAT (h) of Ck(0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose)