Benzo[a]Pyrene Ultralow Dose-Response Study
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Peak Plasma Concentration Cmax
研究概览
简要总结
Evaluation of the pharmacokinetics for [14C]-benzo[a]pyrene ([14C]-BaP) and metabolites in plasma and urine over 48 hours following 4 oral doses of 25, 50, 10 and 250 ng (2.7-27 nCi).
详细描述
The pharmacokinetics for [14C]-BaP and metabolites will be assessed by UHLPC-Accelerator Mass Spectrometry (AMS, Lawrence Livermore National Laboratory) in plasma and urine collected over 48 hours following oral doses of 25, 50, 100 or 250 ng (2.7-27 nCi). Metabolite profiles and kinetics of elimination over this dose range are predicted to be consistent with a BaP physiologically based pharmacokinetic (PBPK) model developed by Pacific Northwest National Laboratory (PNNL). A non-smoker, not exposed occupationally, receives 270-700 ng of BaP daily; about 95% dietary. The WHO has set an estimated safe daily lifetime (70 year/70 Kg individual, cancer endpoint) exposure to BaP of 42-350 ng. This protocol represents de minimus risk.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None (Outcomes Assessor)
盲法说明
Deidentified samples will be analyzed by AMS at Lawrence Livermore National Laboratory and the pharmacokinetics determine at Pacific Northwest National Laboratory.
入排标准
- 年龄范围
- 21 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Inclusion criteria for women:
- •Age 21-65 (inclusive)
- •Must be post-menopausal or have had surgical sterilization to eliminate any possibility for fetal exposure
- •Willing to defer blood donation for one month before, throughout, and one month after completion of study activities
- •Willing to avoid consuming cruciferous vegetables, I3C or DIM supplements, smoked or cured meat or cheeses, or charcoal-grilled meats for 2 weeks prior to and during each study cycle (gas grilled foods acceptable)
- •Inclusion criteria for men:
- •Age 21-65 (inclusive)
- •Willing to defer blood donation for one month before, throughout, and one month after completion of study activities
- •Willing to avoid consuming cruciferous vegetables, I3C or DIM supplements, smoked or cured meat or cheeses, or charcoal-grilled meats for 2 weeks prior to and during each study cycle (gas grilled foods acceptable)
排除标准
- •Exclusion criteria for both men and women:
- •Smoker (tobacco or other substances) or use of smokeless tobacco in past 3 months or living with smoker
- •Regular use of medications that affect gut motility or nutrient absorption (e.g. cholestyramine, sucralfate, orlistat, pro- or anti-motility agents)
- •History of gastrointestinal surgery (e.g. bariatric surgery, cholecystectomy) or gastrointestinal disorder (Crohn's disease, celiac disease, IBS, or colitis)
- •Current or history of kidney or liver disease
- •Prior high-dose 14C exposure from medical tests. (micro-dose 14C exposure not exclusionary)
- •Occupational PAH exposure (e.g. roofers, asphalt pavers, fire-fighters, etc.)
研究组 & 干预措施
25 ng dose, 50 ng dose, 100 ng dose, 250 ng dose
Cycle 1: Capsule containing 25 ng (2.7 nCi) [14C]-benzo[a]pyrene (BaP).
Cycle 2: Capsule containing 50 ng (2.7 nCi) [14C]-benzo[a]pyrene (BaP).
Cycle 3: Capsule containing 100 ng (2.7 nCi) [14C]-benzo[a]pyrene (BaP).
Cycle 4: Capsule containing 250 ng (2.7 nCi) [14C]-benzo[a]pyrene (BaP).
At least 3 weeks will pass between cycles as a washout period.
干预措施: [14C]-benzo[a]pyrene (Drug)
结局指标
主要结局
Peak Plasma Concentration Cmax
时间窗: 0-48 hours for each of the 4 dosing cycles with a washout period of 3 weeks between each dosing cycle
Determination of highest concentration in plasma. Blood samples collected at 0 (baseline), 0.25, 0.5, 1, 2, 3, 4, 8, 24, and 48 hour after dosing. All time points were used to determine peak plasma concentration Cmax.
次要结局
- Time at Highest Plasma Concentration Tmax(0-48 hours for each of the 4 dosing cycles with a washout period of 3 weeks between each dosing cycle)
- Area Under Plasma Concentration Versus Time Curve AUC(0-48 hours for each of the 4 dosing cycles with a washout period of 3 weeks between each dosing cycle)
- Rate of Elimination (k1e)(0-48 hours for each of the 4 dosing cycles with a washout period of 3 weeks between each dosing cycle)
研究者
David Williams
Helen P. Rumbel Professor for Cancer Prevention
Oregon State University