Abstract
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 Cmax 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 Cmax 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.
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Acknowledgments
We would like to thank Osamu Sato of Clinical Research & Development, Otsuka Pharmaceutical Co, Japan, for his help with design of the trial. The editorial support of Upside Endeavors LLC in the preparation of this manuscript was funded by Otsuka America Pharmaceutical, Inc.
Declaration of interest
The authors are employees of Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) or Otsuka Pharmaceutical Co, Japan.
Role of funding source
OPDC provided all funding for the trial.
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Shoaf, S.E., Kim, S.R., Bricmont, P. et al. Pharmacokinetics and pharmacodynamics of single-dose oral tolvaptan in fasted and non-fasted states in healthy Caucasian and Japanese male subjects. Eur J Clin Pharmacol 68, 1595–1603 (2012). https://doi.org/10.1007/s00228-012-1295-5
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DOI: https://doi.org/10.1007/s00228-012-1295-5