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The Pharmacokinetics and Pharmacodynamics of Tolvaptan in Patients with Liver Cirrhosis with Insufficient Response to Conventional Diuretics: a Multicentre, Double-blind, Parallel-group, Phase III Study

2012; SAGE Publishing; Volume: 40; Issue: 6 Linguagem: Inglês

10.1177/030006051204000637

1473-2300

Isao Sakaida, M. Yanase, Yoshio Kobayashi, T Yasutake, Mitsuru Okada, K Okita, Fujito Kageyama, Hiroaki Miyaoka, Hiroki Nakamura, Hiroshi Sakaeda, Kazuya Kariyama, Kenji Takaishi, Kouji Joukou, Makoto Nakamuta, Masahide Oshita, Masahiro Arai, Masaki Mita, Masaki Omoto, Mitsushige Shibatouge, Nobuyoshi Tajiri, Nobuyoshi Tanaka, Satoshi Mochida, Syotaro Sakisaka, Takafumi Ichida, Tetsuro Inokuma, Toshiaki Takayanagi, Toshiji Saibara, Toshiyuki Kimura, Tsukasa Aihara, Yoshio Tokumoto,

Renal function and acid-base balance

This study investigated the pharmacokinetic and pharmacodynamic profile of tolvaptan, and verified its efficacy and safety in patients with liver cirrhosis-associated ascites, with insufficient response to conventional diuretic treatment.This multicentre, double-blind, parallel-group study allocated patients with cirrhosis to receive either 3.75 or 7.5 mg/day tolvaptan orally, once daily, for 7 days. Pharmacokinetic, pharmacodynamic and efficacy variables were measured.Tolvaptan was shown to have high plasma concentrations, and prolonged duration of maximum concentration and half life, in these patients with impaired hepatic function. Tolvaptan resulted in dose-dependent decreases in body weight and ascites volume, and increases in urine output. There were no effects on urinary or serum electrolytes. Tolvaptan was well tolerated, with a good safety profile.Tolvaptan at 3.75 mg/day exerts some effects due to the pharmacokinetic profile in patients with liver cirrhosis. Tolvaptan at 7.5 mg/day is a clinically useful option for treating patients who do not respond well to conventional diuretics.