Oral V2 receptor antagonist (RWJ-351647) in patients with cirrhosis and ascites: a randomized, double-blind, placebo-controlled, single ascending dose study.

Autor: THULUVATH, P. J., MAHESHWARI, A., WONG, F., YOO, H. W., SCHRIER, R. W., PARIKH, C., STEARE, S., KORULA, J.
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Zdroj: Alimentary Pharmacology & Therapeutics; Sep2006, Vol. 24 Issue 6, p973-982, 10p, 4 Charts, 3 Graphs
Abstrakt: Background RWJ-351647 is a selective V2 receptor antagonist that inhibits vasopressin-induced water reabsorption in the kidney. Aim To investigate the safety and tolerability of RWJ-351647 compared with placebo after single oral dose administration to patients with cirrhosis and ascites, on a stable treatment with furosemide and spironolactone. Methods Single oral doses of 1, 2 and 5 mg of RWJ-351647 were administered to 24 patients with ascites on stable concomitant diuretic treatment. Results RWJ-351647 had a tmax of 1 to 1.1 h and mean half-life of 10.4–17.4 h. There was no affect on the pharmacokinetics of concomitant diuretics. Increases in cumulative urine volume and free water excretion, and a decrease in urine osmolality were noted in a dose-dependent manner reaching the statistical significance at the 5-mg dose. Four patients exhibited a decrease of >2 kg in weight in the 24 h after dosing. RWJ-351647 was well tolerated, with no evidence of a dose-related increase in adverse events when compared with placebo. No changes in either serum chemistry or plasma AVP (arginine vasopressin) and renin levels were observed despite the observed aquaresis. Conclusion RWJ-351647 is an effective aquaretic causing dose-dependent increases in urine output and free water clearance, when co-administered with conventional diuretics in patients with cirrhosis and ascites. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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