Pharmacokinetics and Clinical Response of Tolvaptan in Neurocritical Care Patients

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