KetaMoHydBup: Pharmacokinetic Interaction of S-ketamine, Morphine, Hydromorphone and Buprenorphine
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 12
- 主要终点
- Area under the plasma concentration versus time curve (AUC) of morphine, hydromorphone and buprenorphine after intravenous S-ketamine infusion.
研究概览
简要总结
S-ketamine is often administered as a part of multimodal analgesia to reduce postoperative pain and postoperative opioid consumption. Current data indicates that ketamine may be useful for patients with prior use of opioids whereas the benefit for opioid-naive patients is less clear. However, different opioids have variable pharmacokinetic characteristics. Therefore, it is important to evaluate S-ketamine's effect on the pharmacokinetics of opioids.
详细描述
S-ketamine is often used as a part of multimodal analgesia to reduce postoperative pain and opioid consumption, in part by mitigating opioid tolerance and opioid-induced hyperalgesia. However, there are mixed results concerning the effect of ketamine for this indication. Different opioids have various pharmacokinetic characteristics. Ketamine is known to inhibit the liver UGT2B7-enzyme, that is responsible for e.g., morphine metabolism. Therefore, it is important to investigate whether there is a clinically important pharmacokinetic interaction between S-ketamine and opioids metabolized via liver UGT2B7 enzyme. These opioids include morphpine, hydromorphone and buprenoprhine.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This is a double-blind study. Study participants, investigators, care providers and personnel collecting samples are blinded. Personnel preparing study drugs will not participate on conducting the study. On the first phase of the study, study participants will be administered one of the study drug infusions (either S-ketamine or placebo). The order of the study drug is random. On the second phase, study participants will be administered the other study drug (S- ketamine or placebo) that she/he did not receive on the first phase.
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •written informed consent
- •age 18-45 years
- •Normal values in the following laboratory assessments: Hb, P-ALAT, P-AFOS, P-GT, P-creatinine, P-K, P-Na, chemical sample for urine (U-KemSeul). Pregnancy test (P-hCG-tot) must be negative.
- •Urine sample for detection of any illegal drugs must be negative (U-Huum-PS)
- •Normal EKG
- •Normal blood pressure
- •No prior use of illicit drugs
排除标准
- •Tendency/predisposition to illicit drug use, illicit drug use in history
- •Abnormal EKG
- •use of oral contraceptives
- •pregnancy, lactation
- •participating in a less tha 3 months ago
- •Blood donation less than 3 months ago
- •The subject's peripheral veins are hardly visible (predisposing difficulties in cannulation)
- •weight less than 50 kg, body mass index (BMI) less than 18,5 or over 30
研究组 & 干预措施
S-ketamine infusion
12 healthy volunteers, S-ketamine infusion 0.29 mg/kg/h for 4 hours
干预措施: S-ketamine (Drug)
Placebo (NaCl 0.9%) infusion
12 healthy volunteers, placebo (NaCl 0.9%) infusion for 4 hours
干预措施: S-ketamine (Drug)
结局指标
主要结局
Area under the plasma concentration versus time curve (AUC) of morphine, hydromorphone and buprenorphine after intravenous S-ketamine infusion.
时间窗: Time points for the measurements after the initiation of S-ketamine infusion: 0 minutes, 60 minutes, 90 minutes, 120 minutes, 180 minutes and 210 minutes
We aim to investigate whether there is a clinically significant pharmacokinetic interaction between S-ketamine and morphine, S-ketamine and hydromorphone and S-ketamine and buprenorphine.
Half-life time (t1/2) of morphine, hydromorphone and buprenorphine concentrations after intravenous S-ketamine infusion.
时间窗: Time points for assessing half-life time of morphine, hydromorphone and buprenorphine are 0 minutes, 30 minutes, 60 minutes, 90 minutes, 120 minutes, 180 minutes and 210 minutes after initiation of S-ketamine infusion.
We aim to investigate whether there is a clinically significant pharmacokinetic interaction between S-ketamine, morphine, S-ketamine and hydromorphone and S-ketamine and buprenorphine.
Peak plasma concentrations (Cmax) of morphine, hydromorphone and buprenorphine after intravenous S-ketamine infusion
时间窗: Time points for assessing peak plasma concentrations (Cmax) for morphine, hydromorphone and buprenorphine are the following: 0 minutes, 30 minutes, 60 minutes, 90 minutes, 120 minutes, 180 minutes, 210 minutes after the initiation of S-ketamine infusion.
We aim to investigate whether there is a clinically significant pharmacokinetic interaction between S-ketamine, morphine, S-ketamine and hydromorphone and S-ketamine and buprenorphine.
次要结局
- The effect of S-ketamine infusion on cortisol release.(Time points for assessments: 30 minutes, 120 minutes, 240 minutes, 360 minutes, 480 minutes and at Day1 after the intiation of S-ketamine infusion)
- The effect of S-ketamine on brain-derived neurotrophic factor (BDNF) release(Time points for assessments: 30 minutes, 120 minutes, 240 minutes, 360 minutes, 480 minutes and at Day1 after the intiation of S-ketamine infusion)
- The effect of S-ketamine infusion on prolactin release.(Time points for assessments: 30 minutes, 120 minutes, 240 minutes, 360 minutes, 480 minutes and at Day1 after the intiation of S-ketamine infusion)
- The effect of S-ketamine on vascular endothelial growth factor (VEGF) release(Time points for assessments: 30 minutes, 120 minutes, 240 minutes, 360 minutes, 480 minutes and at Day1 after the intiation of S-ketamine infusion.)
- The effect of S-ketamine infusion on thrombocyte aggregation.(At 2 hours after initiation of S-ketamine infusion.)
研究者
Elina Brinck
MD, PhD
Helsinki University Central Hospital