Tolvaptan is one of new class of medications approved for treatment of low blood sodium
(hyponatremia). It works by interfering with the effect of the antidiuretic hormone,
vasopressin, thereby increasing urine output and decreasing body water. However, the
magnitude of these effects vary from person to person. Thus, the efficacy of tolvaptan is
less reliable than an infusion of a concentrated salt solution for emergency, short term
treatment of hyponatremia.
This study is designed to test 3 hypotheses about the variable efficacy of tolvaptan.
1. The variable effect on urine output is due to individual differences in blood
vasopressin which counteracts the effects of tolvaptan.
2. The differences in blood vasopressin are due to individual differences in the amount
secreted in response to a rise in blood sodium.
3. The variable effect on blood sodium is due mainly to the variable effect on urine output
and can be corrected by maintaining water intake below urine output.
The study has 2 parts and will be performed in 12 healthy adult males.
1. Six subjects will receive tolvaptan at a dose of 60 mg by mouth and six subjects will
receive tolvaptan at 30 mg by mouth. Blood and urine will be collected hourly for 6
hours and water will be ingested in prescribed amounts. For the next 16 hours, subjects
will drink at will and blood and urine will be collected 4 more times.
2. One week later, the same subjects will receive a concentrated salt solution (3% saline)
by vein for 6 hours. During this time, blood and urine will be collected hourly but
drinking will not be permitted. For the next 4 hours, subjects will be allowed to drink
at will while blood and urine are collected twice more.
The volume, concentration and creatinine content of each urine will be determined. Blood will
be analyzed for sodium, vasopressin and, in the first study, tolvaptan.