Abstract | BACKGROUND: AIM: 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.
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Authors | P J Thuluvath, A Maheshwari, F Wong, H W Yoo, R W Schrier, C Parikh, S Steare, J Korula |
Journal | Alimentary pharmacology & therapeutics
(Aliment Pharmacol Ther)
Vol. 24
Issue 6
Pg. 973-82
(Sep 15 2006)
ISSN: 0269-2813 [Print] England |
PMID | 16948809
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antidiuretic Hormone Receptor Antagonists
- Diuretics
- RWJ-351647
- Arginine Vasopressin
- Benzodiazepines
- Spironolactone
- Furosemide
- Sodium
- Renin
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Topics |
- Administration, Oral
- Adult
- Antidiuretic Hormone Receptor Antagonists
- Arginine Vasopressin
(blood)
- Ascites
(drug therapy)
- Benzodiazepines
(administration & dosage, adverse effects, pharmacokinetics)
- Diuretics
(pharmacokinetics, therapeutic use)
- Dose-Response Relationship, Drug
- Double-Blind Method
- Drug Administration Schedule
- Female
- Furosemide
(pharmacokinetics, therapeutic use)
- Humans
- Liver Cirrhosis
(drug therapy)
- Male
- Middle Aged
- Osmolar Concentration
- Renin
(blood)
- Sodium
(blood)
- Spironolactone
(pharmacokinetics, therapeutic use)
- Treatment Outcome
- Urination
(drug effects)
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