Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 973-982 |
| Number of pages | 10 |
| Journal | Alimentary Pharmacology and Therapeutics |
| Volume | 24 |
| Issue number | 6 |
| DOIs | |
| State | Published - Sep 1 2006 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Pharmacology (medical)
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Oral V2 receptor antagonist (RWJ-351647) in patients with cirrhosis and ascites : A randomized, double-blind, placebo-controlled, single ascending dose study. / Thuluvath, P. J.; Maheshwari, A.; Wong, F.; Yoo, H. W.; Schrier, R. W.; Parikh, Chirag; Steare, S.; Korula, J.
In: Alimentary Pharmacology and Therapeutics, Vol. 24, No. 6, 01.09.2006, p. 973-982.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Oral V2 receptor antagonist (RWJ-351647) in patients with cirrhosis and ascites
T2 - A randomized, double-blind, placebo-controlled, single ascending dose study
AU - Thuluvath, P. J.
AU - Maheshwari, A.
AU - Wong, F.
AU - Yoo, H. W.
AU - Schrier, R. W.
AU - Parikh, Chirag
AU - Steare, S.
AU - Korula, J.
PY - 2006/9/1
Y1 - 2006/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33748310551&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748310551&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2036.2006.03088.x
DO - 10.1111/j.1365-2036.2006.03088.x
M3 - Article
C2 - 16948809
AN - SCOPUS:33748310551
VL - 24
SP - 973
EP - 982
JO - Alimentary Pharmacology and Therapeutics
JF - Alimentary Pharmacology and Therapeutics
SN - 0269-2813
IS - 6
ER -