Pharmacokinetics and Clinical Response of Tolvaptan in Neurocritical Care Patients

University of North Carolina, Chapel Hill1 enrolled

Overview

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

Study Type

OBSERVATIONAL

Enrollment

Conditions

Brain Injury Hyponatremia

Interventions

TolvaptanDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. 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 2. Informed consent obtained from patient or authorized legal representative 3. Age ≥ 18 years Exclusion Criteria: 1. Use of CYP3A4 inhibitors or inducers as medications, juices, or herbal supplements within 96 hours prior to the study period. 2. A positive urine or serum pregnancy test, or are currently breast-feeding 3. Patients with subarachnoid hemorrhage or in patients suspected to have cerebral salt wasting or any signs of volume depletion 4. Imminent death or brain death 5. Concomitant fungal infection 6. History of HIV 7. Concomitant administration of continuous infusion hypertonic saline, conivaptan or hypertonic saline bolus within 24 hours of study drug administration 8. Diuretic or mannitol administration within 6 hours 9. Serum creatinine ≥ 3.5 mg/dL 10. Diagnosis of cirrhosis or liver function tests \> 2x the upper limit of normal

Locations (3)

Barnes-Jewish Hospital

St Louis, Missouri, United States

University of North Carolina Hospitals

Chapel Hill, North Carolina, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Outcomes

Primary Outcomes

Maximum observed plasma concentration (Cmax) and time to maximum observed plasma concentration (Tmax) of tolvaptan over 36 hours post-dose

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.