The Effects of BCRP Q141K on Allopurinol Pharmacokinetics and Dynamics
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Percent Change Uric Acid
研究概览
简要总结
Subjects will undergo a placebo and allopurinol phase to better understand the effects of the reduced function BCRP Q141K variant on allopurinol pharmacokinetics and pharmacodynamics.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •self-identified as Asian/European ancestry
- •generally healthy with approved lab values for CBC,HFP,RFP, and uric acid
- •Subjects with the ABCG2 genotype, homozygous, heterozygous or homozygous for the major allele of rs2231142 will be recruited
排除标准
- •vascular disease
- •renal impairment
- •medications/supplements that affect uric acid levels
- •pregnant or lactating women
- •prior history of allergic reaction to allopurinol or testing positive for HLA-B*5801 allele
- •risk of urinary or gastric retention or narrow-angle glaucoma
- •impaired hepatic function
- •evidence of anemia
- •evidence or diagnosis of congestive heart failure
- •subjects with a mutation other than rs2231142 in the ABCG2 genotype
- •subjects taking hormonal contraceptives or other hormonal medications
- •evidence of recreational drug use as determined by questionnaire
研究组 & 干预措施
BCRP Q141K CC
Participants that are homozygous reference for BCRP Q141K receive at least one 300 mg dose of allopurinol followed by blood/urine collection for up to 72 hours post-dose.
干预措施: Allopurinol (Drug)
BCRP Q141K CC
Participants that are homozygous reference for BCRP Q141K receive at least one 300 mg dose of allopurinol followed by blood/urine collection for up to 72 hours post-dose.
干预措施: Placebo (Other)
BCRP Q141K CA
Participants that are heterozygous for the BCRP Q141K allele receive at least one 300 mg dose of allopurinol, with blood/urine collections up to 72 hours post-dose.
干预措施: Allopurinol (Drug)
BCRP Q141K CA
Participants that are heterozygous for the BCRP Q141K allele receive at least one 300 mg dose of allopurinol, with blood/urine collections up to 72 hours post-dose.
干预措施: Placebo (Other)
BCRP Q141K AA
Participants homozygous for the BCRP Q141K allele receive at least one 300 mg dose of allopurinol with blood/urine collection for up to 72 hours post-dose.
干预措施: Allopurinol (Drug)
BCRP Q141K AA
Participants homozygous for the BCRP Q141K allele receive at least one 300 mg dose of allopurinol with blood/urine collection for up to 72 hours post-dose.
干预措施: Placebo (Other)
结局指标
主要结局
Percent Change Uric Acid
时间窗: 24 hours
Maximum percent change in uric acid after a single dose of allopurinol
Oxypurinol Renal Clearance
时间窗: 24 hours (Urine collected 0-4 hrs,4-8 hrs,8-10 hrs,10-24 hrs post-dose)
Renal clearance as defined by amount excreted in 24 hours/AUC from 0-24 hours
次要结局
- Oxypurinol AUC(24 hours (Collections at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 24 hours post-dose))