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 tolvapt...

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Publicado en:European Journal of Clinical Pharmacology Vol. 68; no. 12; pp. 1595 - 1604
Autores principales: Shoaf, Susan, Kim, Seong, Bricmont, Patricia, Mallikaarjun, Suresh
Formato: research tables/charts Journal Article
Publicado: Springer Nature Dec2012
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Dec2012
      vid: 68
      iid: 12
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s00228-012-1295-5
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        atl: Pharmacokinetics and pharmacodynamics of single-dose oral tolvaptan in fasted and non-fasted states in healthy Caucasian and Japanese male subjects.
      aug:
        au:
          Shoaf, Susan
          Kim, Seong
          Bricmont, Patricia
          Mallikaarjun, Suresh
        affil: Clinical Pharmacology, Otsuka Pharmaceutical Development & Commercialization, Inc, 2440 Research Blvd. Rockville 20850 USA
      sug:
        subj:
          Metabolism
          Ethnology
          White Persons
          Japanese Persons
          Heterocyclic Compounds Pharmacokinetics
          Heterocyclic Compounds Pharmacodynamics
          Hyponatremia Drug Therapy
          Food Intake
          Crossover Design
          Preprocedural Fasting
          Male
          Human
          Descriptive Statistics
          Confidence Intervals
          Heterocyclic Compounds Urine
          Heterocyclic Compounds Blood
          Young Adult
          Adult
          Middle Age
          Random Assignment
          Linear Regression
          Chromatography, High Pressure Liquid
          Adverse Drug Event
          Funding Source
          Adult: 19-44 years
          Middle Aged: 45-64 years
          Male
      ab: 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 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 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.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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