A multicenter, open-label, dose-ranging study to exploratively evaluate the efficacy, safety, and dose-response of tolvaptan in patients with decompensated liver cirrhosis.
OBJECTIVE
We examined the efficacy of tolvaptan, an orally effective nonpeptide vasopressin V(2) receptor antagonist, in a Japanese clinical study in patients with intractable ascites and/or lower limb edema associated with decompensated liver cirrhosis.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Tolvaptan dose-dependently decreased body weight and abdominal circumference and improved ascites and edema beginning from 15 mg, demonstrating a potent aquaretic effect.
Okita
Kiwamu
K
Social Insurance Alliance Shimonoseki Kohsei Hospital, 3-3-8 Kamishinchi-cho, Shimonoseki, Yamaguchi 750-0061, Japan. k.okita@kousei-h.jp
Sakaida
Isao
I
Okada
Mitsuru
M
Kaneko
Akira
A
Chayama
Kazuaki
K
Kato
Michio
M
Sata
Michio
M
Yoshihara
Harumasa
H
Yoshihara
Naomasa
N
Ono
Noriyuki
N
Murawaki
Yoshikazu
Y
D000284:Administration, Oral; D065092:Antidiuretic Hormone Receptor Antagonists; D001201:Ascites / Q000188:drug therapy / Q000209:etiology; D001552:Benzazepines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy / Q000209:etiology; D005260:Female; D005665:Furosemide / Q000627:therapeutic use; D006801:Humans; D007564:Japan; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D035002:Lower Extremity; D008297:Male; D008875:Middle Aged; D000077602:Tolvaptan; D016896:Treatment Outcome; D055105:Waist Circumference / Q000187:drug effects
D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D000077602:Tolvaptan; D005665:Furosemide
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