Hyponatremia is the most commonly encountered electrolyte abnormality. If uncorrected, it can lead to seizure, coma, or death due to brain stem herniation. Once the serum osmolality and volume status of the patient is determined, treatment should be initiated to correct the serum sodium by 8 to 12 mEq/L within the first 24 hours. Arginine vasopressin (AVP) antagonists represent a new class of drugs indicated to treat hypervolemic and euvolemic hyponatremia. Conivaptan is a nonselective AVP antagonist that is available intravenously, and tolvaptan is a V2 selective AVP antagonist that is available as an oral tablet. Both agents produce highly effective and safe aquaresis to increase serum Na levels. Both agents have limited data in heart failure patients, but have been shown to produce significant decreases in pulmonary capillary wedge pressure, body weight, and signs and symptoms of heart failure. Neither drug has been approved for the treatment of heart failure, to date. There were no cases of osmotic demyelination syndrome with these agents, and the most common adverse events during studies were dry mouth and thirst. Overall, both conivaptan and tolvaptan are promising agents that can be used in hospitalized patients. Further studies are needed to assess the appropriateness of their use in symptomatic hyponatremic patients, and to determine their benefits in terms of disease outcome and length of stay to justify the high acquisition costs.
[Show abstract][Hide abstract] ABSTRACT: Twenty-six possible as well as observed impurities during the preparation of Tolvaptan have been identified, prepared, and characterized by HPLC (high performance liquid chromatography), NMR (nuclear magnetic resonance), and mass spectra. Control of these impurities, formed during various stages of Tolvaptan preparation, has been mentioned in this paper.
[Show abstract][Hide abstract] ABSTRACT: Acute decompensated heart failure (ADHF) is a common syndrome with diverse etiologies and precipitating factors, which is associated with significant morbidity and mortality. Tremendous resources are used in treating this syndrome, with few prospectively designed clinical trials to guide therapy. Patients suffering from ADHF are at increased risk for readmission to the hospital as well as an increased risk of death. Prompt identification and management of these patients can lead to shorter length of hospital stay, lower likelihood of readmission, and, perhaps, lower mortality. Initial treatment should target the relief of congestive symptoms. Intravenous loop diuretics are the mainstay of therapy, whereas ultrafiltration has emerged as a viable option in patients refractory to conventional treatment with diuretics. The safety and efficacy of nesiritide have been clarified in a recent large randomized trial, reassuring a favorable safety profile, but with modest improvement in short-term clinical outcomes. Thus, the preferred intravenous vasoactive medication has yet to be determined in large clinical trials, and positive inotropic agents should be reserved for patients with hemodynamic collapse. This article reviews the in-hospital assessment and management of ADHF.
Cardiology in review 01/2011; 19(3):122-9. DOI:10.1097/CRD.0b013e318214022b · 2.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tolvaptan is a selective vasopressin V2 receptor antagonist that can be given orally once daily for treatment of clinically significant hypervolemic and euvolemic hyponatremia (US and Europe) or extracellular volume expansion despite taking other diuretics (Japan). In vitro studies indicated that tolvaptan was a CYP3A4 substrate.
A single-center, randomized, crossover trial of 60-mg tolvaptan with 240 mL of water or with 240 mL of reconstituted grapefruit juice (washout period of 72 h between doses) was conducted in 20 healthy subjects. Blood samples for tolvaptan plasma concentrations were obtained for 48 h postdose.
All subjects completed the trial. Following co-administration with grapefruit juice, tolvaptan concentrations were elevated compared with tolvaptan alone for only 16 h postdose; consequently, the mean elimination half-life of tolvaptan was unchanged, 5.7 vs 5.1 h respectively. The mean maximal plasma concentration (C(max)) and the area under the curve (AUC(∞)) of tolvaptan were increased 1.86- and 1.56-fold respectively when co-administered with grapefruit juice.
It appears that grapefruit juice increases the bioavailability of tolvaptan, but does not affect its systemic elimination. The adverse event profile was consistent with the aquaretic effect of tolvaptan as urinary frequency, thirst, and dry mouth were the most frequently reported events.
European Journal of Clinical Pharmacology 08/2011; 68(2):207-11. DOI:10.1007/s00228-011-1106-4 · 2.97 Impact Factor
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