Pharmacokinetics and Clinical Response of Tolvaptan in Neurocritical Care Patients
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 3
- 主要终点
- The elimination rate constant (ke) of tolvaptan over 36 hours post-dose
研究概览
简要总结
To assess the pharmacokinetic profile of tolvaptan in critically ill acute brain injury patients and to secondarily evaluate the clinical response and safety of tolvaptan in acute brain injured patients
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Acute brain injury patients in the ICU with hyponatremia (Na < 135 mmol/L) necessitating treatment in addition to fluid restriction per clinical judgement or patients at risk for worsening cerebral edema
- •Informed consent obtained from patient or authorized legal representative
- •Age ≥ 18 years
排除标准
- •Use of CYP3A4 inhibitors or inducers as medications, juices, or herbal supplements within 96 hours prior to the study period.
- •A positive urine or serum pregnancy test, or are currently breast-feeding
- •Patients with subarachnoid hemorrhage or in patients suspected to have cerebral salt wasting or any signs of volume depletion
- •Imminent death or brain death
- •Concomitant fungal infection
- •History of HIV
- •Concomitant administration of continuous infusion hypertonic saline, conivaptan or hypertonic saline bolus within 24 hours of study drug administration
- •Diuretic or mannitol administration within 6 hours
- •Serum creatinine ≥ 3.5 mg/dL
- •Diagnosis of cirrhosis or liver function tests > 2x the upper limit of normal
研究组 & 干预措施
Brain injured patients with hyponatremia
Patients with acute brain injury who develop hyponatremia and are administered tolvaptan via the nasogastric tube, deemed necessary by the primary medical team.
干预措施: Tolvaptan (Drug)
结局指标
主要结局
The elimination rate constant (ke) of tolvaptan over 36 hours post-dose
时间窗: Over 36 hours from drug administration
Ke derived from plasma concentrations versus time using a validated LS/MS/MS assay is sodium heparinized plasma. The tolvaptan assay has a range of 1.00 - 200 mg/mL. Blood samples will be collected at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30 and 36 hours after the dose of tolvaptan is administered. The first 15 patients will receive single dose 15mg of tolvaptan via a gastric tube and if determined not bioequivalent and no clinical response to oral administration and safe to administer, then last 15 patients will receive 30mg single dose via a gastric tube.
Area under the plasma concentration time curve (AUC) of tolvaptan from time zero to 36 hours post-dose
时间窗: Over 36 hours from drug administration
AUC will be computed from 0 to 36 hours using the linear-log trapezoidal method and extrapolated to infinity. Tolvaptan concentrations will be determined using a validated LS/MS/MS assay is sodium heparinized plasma. The tolvaptan assay has a range of 1.00 - 200 mg/mL. Blood samples will be collected at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30 and 36 hours after the dose of tolvaptan is administered. The first 15 patients will receive single dose 15mg of tolvaptan via a gastric tube and if determined not bioequivalent and no clinical response to oral administration and safe to administer, then last 15 patients will receive 30mg single dose via a gastric tube.
Maximum observed plasma concentration (Cmax) and time to maximum observed plasma concentration (Tmax) of tolvaptan over 36 hours post-dose
时间窗: Over 36 hours from drug administration
Cmax will be derived from plasma concentrations versus time using a validated LS/MS/MS assay is sodium heparinized plasma. The tolvaptan assay has a range of 1.00 - 200 mg/mL. Blood samples will be collected at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30 and 36 hours after the dose of tolvaptan is administered. The first 15 patients will receive single dose 15mg of tolvaptan via a gastric tube and if determined not bioequivalent and no clinical response to oral administration and safe to administer, then last 15 patients will receive 30mg single dose via a gastric tube.
次要结局
- The safety of tolvaptan administered via a nasogastric tube in acute brain injured patients(Over 36 hours from drug administration)
- The clinical response of tolvaptan administered through the nasogastric tube in acute brain injured patients(Over 36 hours from drug administration)