Journal of Gastroenterology

, Volume 45, Issue 9, pp 979–987 | Cite as

A multicenter, open-label, dose-ranging study to exploratively evaluate the efficacy, safety, and dose–response of tolvaptan in patients with decompensated liver cirrhosis

  • Kiwamu OkitaEmail author
  • Isao Sakaida
  • Mitsuru Okada
  • Akira Kaneko
  • Kazuaki Chayama
  • Michio Kato
  • Michio Sata
  • Naomasa Yoshihara
  • Noriyuki Ono
  • Yoshikazu Murawaki
Original Article—Liver, Pancreas, and Biliary Tract



We examined the efficacy of tolvaptan, an orally effective nonpeptide vasopressin V2 receptor antagonist, in a Japanese clinical study in patients with intractable ascites and/or lower limb edema associated with decompensated liver cirrhosis.


Tolvaptan was orally administrated at titrated doses of 15, 30, and 60 mg once daily after breakfast for 3 days at each dose to 18 liver cirrhosis patients with persistent ascites and/or lower limb edema despite receiving oral furosemide at 40 mg/day or higher.


Decreased body weight and abdominal circumference and improvement of ascites and edema were observed following tolvaptan administration beginning from 15 mg. Composite ascites/edema improvement rate was 88.2% at individual maximum doses and 64.7, 80.0, and 90.9%, respectively, after 3-day administration at 15, 30, and 60 mg. Changes in body weight after 3-day administration at 15, 30, and 60 mg were −1.6 ± 0.9, −2.6 ± 1.2, and −3.4 ± 2.1 kg (mean ± SD), respectively, and decreases of 1 kg or more were seen from day 2 (24 h after first dosing). Changes in abdominal circumference ranged from −2.8 to −6.0 cm. Cumulative 24-h urine volumes after 3-day administration at 15, 30, and 60 mg were, respectively, 3240.3 ± 1014.5, 3943.3 ± 1060.6, and 4537.4 ± 1621.3 mL/day (mean ± SD). Urine osmolarity was markedly decreased and remained decreased until the end of treatment.


Tolvaptan dose-dependently decreased body weight and abdominal circumference and improved ascites and edema beginning from 15 mg, demonstrating a potent aquaretic effect.


Tolvaptan (OPC-41061) Vasopressin V2 receptor antagonist Decompensated liver cirrhosis Intractable ascites Leg edema 



The authors are most grateful to their fellow researchers and hospitals for their contribution to data collection.


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Copyright information

© Springer 2010

Authors and Affiliations

  • Kiwamu Okita
    • 1
    Email author
  • Isao Sakaida
    • 2
  • Mitsuru Okada
    • 3
  • Akira Kaneko
    • 4
  • Kazuaki Chayama
    • 5
  • Michio Kato
    • 6
  • Michio Sata
    • 7
  • Naomasa Yoshihara
    • 8
  • Noriyuki Ono
    • 9
  • Yoshikazu Murawaki
    • 10
  1. 1.Social Insurance Alliance Shimonoseki Kohsei HospitalShimonosekiJapan
  2. 2.Department of Gastroenterology and HepatologyYamaguchi University Graduate School of MedicineUbeJapan
  3. 3.Otsuka Pharmaceutical Co., Ltd.OsakaJapan
  4. 4.Department of Internal MedicineNTT West Osaka HospitalOsakaJapan
  5. 5.Division of Frontier Medical Science, Department of Molecular Science, Programs for Biomedical Research, Graduate School of Biomedical ScienceHiroshima UniversityHiroshimaJapan
  6. 6.Department of GastroenterologyNational Hospital Organization Minami Wakayama Medical CenterTanabeJapan
  7. 7.Division of Gastroenterology, Department of MedicineKurume University School of MedicineKurumeJapan
  8. 8.Department of Internal MedicineOsaka Rosai HospitalOsakaJapan
  9. 9.Department of General Medical CareChikugo City HospitalChikugoJapan
  10. 10.Department of Internal MedicineTottori University Medical School HospitalTottoriJapan

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