Pharmacokinetics and pharmacodynamics of single-dose oral tolvaptan in fasted and non-fasted states in healthy Caucasian and Japanese male subjects.

PURPOSE

To compare the pharmacokinetics and pharmacodynamics of tolvaptan in Caucasian and Japanese healthy male subjects under fasting and non-fasting conditions.

METHODS

This was a single-center, parallel-group, randomized, open-label, three-period crossover trial of single oral doses of tolvaptan 30 mg under fasting and non-fasting [a high-fat, high-calorie meal (HFM) or Japanese standard meal] conditions in 25 healthy male Caucasian subjects and 24 healthy male Japanese subjects. Pharmacodynamic endpoints were urine volume and fluid balance for 0 to 24 h postdose.

RESULTS

In the fasted state, the plasma tolvaptan C(max) and AUC(∞) geometric mean ratios (90 % confidence interval) were 1.105 (0.845-1.444) and 1.145 (0.843-1.554) for Japanese compared to Caucasian subjects. A HFM increased the C(max) and AUC(∞) values by about 1.15-fold in both Japanese and Caucasian subjects.. Twenty-four-hour urine volumes paralleled pharmacokinetic changes, but the increases were not clinically significant. Fluid balance in the Japanese men was 1.4- to 2.0-fold more negative than that in the Caucasian men.

CONCLUSION

Tolvaptan pharmacokinetics is not clinically significantly affected by race. Body weight is a factor that affects exposure. Tolvaptan can be administered with or without food.