Rebello Candida J, Beyl Robbie A, Lertora Juan J L, Greenway Frank L, Ravussin Eric, Ribnicky David M, Poulev Alexander, Kennedy Brandon J, Castro Hector F, Campagna Shawn R, Coulter Ann A, Redman Leanne M
Pharmacology Clinical Trials, Pennington Biomedical Research Centre, Baton Rouge, Louisiana.
Biostatistics, Pennington Biomedical Research Centre, Baton Rouge, Louisiana.
Diabetes Obes Metab. 2020 Jan;22(1):91-98. doi: 10.1111/dom.13868. Epub 2019 Sep 30.
To evaluate the safety and pharmacokinetics of naringenin in healthy adults consuming whole-orange (Citrus sinensis) extract.
In a single-ascending-dose randomized crossover trial, 18 adults ingested doses of 150 mg (NAR150), 300 mg (NAR300), 600 mg (NAR600) and 900 mg (NAR900) naringenin or placebo. Each dose or placebo was followed by a wash-out period of at least 1 week. Blood safety markers were evaluated pre-dose and 24 hours post-dose. Adverse events (AEs) were recorded. Serum naringenin concentrations were measured before and over 24 hours following ingestion of placebo, NAR150 and NAR600. Four- and 24-hour serum measurements were obtained after placebo, NAR300 and NAR900 ingestion. Data were analysed using a mixed-effects linear model.
There were no relevant AEs or changes in blood safety markers following ingestion of any of the naringenin doses. The pharmacokinetic variables were: maximal concentration: 15.76 ± 7.88 μM (NAR150) and 48.45 ± 7.88 μM (NAR600); time to peak: 3.17 ± 0.74 hours (NAR150) and 2.41 ± 0.74 hours (NAR600); area under the 24-hour concentration-time curve: 67.61 ± 24.36 μM × h (NAR150) and 199.05 ± 24.36 μM × h (NAR600); and apparent oral clearance: 10.21 ± 2.34 L/h (NAR150) and 13.70 ± 2.34 L/h (NAR600). Naringenin half-life was 3.0 hours (NAR150) and 2.65 hours (NAR600). After NAR300 ingestion, serum concentrations were 10.67 ± 5.74 μM (4 hours) and 0.35 ± 0.30 μM (24 hours). After NAR900 ingestion, serum concentrations were 43.11 ± 5.26 μM (4 hours) and 0.24 ± 0.30 μM (24 hours).
Ingestion of 150 to 900 mg doses of naringenin is safe in healthy adults, and serum concentrations are proportional to the dose administered. Since naringenin (8 μM) is effective in primary human adipocytes, ingestion of 300 mg naringenin twice/d will likely elicit a physiological effect.
评估健康成年人食用全橙（甜橙）提取物后柚皮素的安全性和药代动力学。
在一项单剂量递增随机交叉试验中，18名成年人分别摄入150毫克（NAR150）、300毫克（NAR300）、600毫克（NAR600）和900毫克（NAR900）的柚皮素或安慰剂。每次给药或服用安慰剂后均有至少1周的洗脱期。在给药前和给药后24小时评估血液安全指标。记录不良事件（AE）。在摄入安慰剂、NAR150和NAR600后，于摄入前及摄入后24小时内测量血清柚皮素浓度。在摄入安慰剂、NAR300和NAR900后，进行4小时和24小时的血清测量。使用混合效应线性模型分析数据。
摄入任何剂量的柚皮素后，均未出现相关不良事件或血液安全指标变化。药代动力学变量如下：最大浓度：15.76±7.88微摩尔/升（NAR150）和48.45±7.88微摩尔/升（NAR600）；达峰时间：3.17±0.74小时（NAR150）和2.41±0.74小时（NAR600）；24小时浓度-时间曲线下面积：67.61±24.36微摩尔·小时（NAR150）和199.05±24.36微摩尔·小时（NAR60０）；表观口服清除率：10.21±2.34升/小时（NAR150）和13.70±2.34升/小时（NAR600）。柚皮素半衰期在NAR150组为3.0小时，在NAR600组为2.65小时。摄入NAR300后，血清浓度在4小时时为10.67±5.74微摩尔/升，24小时时为0.35±0.30微摩尔/升。摄入NAR900后，血清浓度在4小时时为43.11±5.26微摩尔/升，24小时时为0.24±0.30微摩尔/升。
健康成年人摄入150至900毫克剂量的柚皮素是安全的，且血清浓度与给药剂量成正比。由于柚皮素（8微摩尔/升）对原代人脂肪细胞有效，每天两次摄入300毫克柚皮素可能会产生生理效应。
