A Single Centre Prospective Randomised Study to Investigate the Cerebrospinal Fluid (CSF) Pharmacokinetics of Intravenous Paracetamol in Humans
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Measurement of AM404 in CSF
研究概览
简要总结
Despite its use for decades all over the world, the exact mechanism of action of paracetamol is not fully understood and essentially involves a combination of hypotheses. It is known to have an effect via the central nervous system, and of the many mechanisms proposed, one hypothesis is that it may have indirectly activate CB1 (cannabinoid) receptors, through its novel metabolite AM404.
This study aims to elucidate cerebrospinal levels of paracetamol and to measure the concentration of its metabolites, including AM404 in CSF. This may, in turn, give us useful information on the mechanism of action of paracetamol.
详细描述
Patients undergoing spinal blockade for urological surgery were administered 1g paracetamol intravenously at varying intervals prior to spinal anaesthesia, at which time 5mls of cerebrospinal fluid and 10mls of blood were sampled, and analysed for concentrations of paracetamol, paracetamol glucuronide, paracetamol sulphate, and AM404, a known endocannabinoid reuptake inhibitor, and metabolite of paracetamol.
Paracetamol readily penetrates into the cerebrospinal fluid in animal studies and in children. This could account for the rapid central analgesic and antipyretic action of intravenous paracetamol however this remains to be studied in adults. AM404 has never before been identified in humans, and its presence in CSF following paracetamol supports the hypothesis of a central mechanism of action of paracetamol via AM404.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult subjects aged 18 to 80 years
- •Subjects undergoing surgery who require a spinal anaesthetic and paracetamol as part of their routine anaesthetic plan
- •Subjects with an American Society of Anesthesiology score of I-III
排除标准
- •Subjects with any contraindication to spinal anaesthesia
- •Subjects with known clotting abnormalities
- •Pregnant or lactating women
- •Subjects with known hypersensitivity to paracetamol
- •Patients with severe hepatocellular insufficiency
- •Patients already taking regular doses of paracetamol
- •Any subjects deemed medically unsuitable by the investigator
研究组 & 干预措施
Sampling at approx 15 minutes
Plasma and CSF samples to be taken at 15 minutes post administration of intravenous paracetamol
干预措施: Administration of paracetamol (Drug)
Sampling at approx 30 minutes
Plasma and CSF samples to be taken at 30 minutes post administration of intravenous paracetamol
干预措施: Administration of paracetamol (Drug)
Sampling at approx 120minutes
Plasma and CSF samples to be taken at 120 minutes post administration of intravenous paracetamol
干预措施: Administration of paracetamol (Drug)
结局指标
主要结局
Measurement of AM404 in CSF
时间窗: 5-211 minutes post-administration of paracetamol
AM404 is a metabolite of paracetamol thought to be formed in the brain.
次要结局
- Measurement of paracetamol in plasma and CSF(5-211 minutes post administration of paracetamol)
- Measurement of paracetamol glucuronide and sulphate conjugates in plasma and CSF.(5-211 minutes post administration of paracetamol)