Phase III clinical pharmacology study of tolvaptan.

PURPOSE: This study aimed to investigate the pharmacokinetics, pharmacodynamics, efficacy and safety of tolvaptan, an orally effective vasopressin V2-receptor antagonist.

METHODS

This was a multicenter, randomized, double-blind, parallel group study. Tolvaptan was administered at 7.5 or 15 mg, in combination with furosemide, for 7 days in Japanese heart failure (HF) patients with volume overload that had not resolved despite receiving furosemide.

RESULTS

The blood concentration of tolvaptan was maintained at a higher concentration for a longer time in patients who received 15 mg/day when compared with patients who received 7.5 mg/day. Tolvaptan increased urine volume and increased weight loss dose-dependently when used in combination with furosemide. Importantly, tolvaptan enhanced water diuresis without affecting blood electrolyte levels.

CONCLUSION

Tolvaptan exerts diuretic effects and causes body weight loss at the low dose of 7.5 mg; however, these effects were less than those elicited by 15 mg tolvaptan.