Department of Internal Medicine, Hanyang University Guri Hospital, Guri, Korea.
Department of Internal Medicine, Chonbuk National University School of Medicine, Jeonju, Korea.
J Korean Med Sci. 2018 Apr 9;33(15):e112. doi: 10.3346/jkms.2018.33.e112.
The aim of this multicenter study was to evaluate the safety and efficacy of tolvaptan (TLV) in Korean patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH).
Of 51 enrolled patients with SIADH, 39 patients (16 female patients, aged 70.8 ± 11.3 years) were included in an intention to treat analysis. All patients received 15 mg/day as the initial dose, and the dose was then increased up to 60 mg/day (as needed) until day 4.
Serum sodium increased significantly from baseline during the first 24 hours (126.8 ± 4.3 vs. 133.7 ± 3.8 mmol/L, P < 0.001), rose gradually between days 1 and 4 (133.7 ± 3.8 vs. 135.6 ± 3.6 mmol/L, P < 0.05), and then plateaued until day 11 (136.7 ± 4.5 mmol/L). The correlation between the change in serum sodium for the first 24 hours and initial serum sodium concentration was significant (r = -0.602, P < 0.001). In severe hyponatremia (< 125 mmol/L), the change was significantly higher (11.1 ± 4.8 mmol/L) than in moderate (6.4 ± 2.5 mmol/L, P < 0.05) or mild hyponatremia (4.3 ± 3.3 mmol/L, P < 0.01). In addition, logistic regression analysis showed that body weight (odds ratio [OR], 0.858; 95% confidence interval [CI], 0.775-0.976; P = 0.020) and body mass index (BMI) (OR, 0.692; 95% CI, 0.500-0.956; P = 0.026) were associated with rapid correction. No serious adverse events were reported, but in 13% of patients hyponatremia was overcorrected.
TLV is effective in correcting hyponatremia and well-tolerated in Korean patients with SIADH. However, those with low body weight, low BMI or severe hyponatremia, could be vulnerable to overcorrection with the initial dose of 15 mg TLV.
本多中心研究旨在评估托伐普坦（TLV）在患有抗利尿激素不适当分泌综合征（SIADH）的韩国患者中的安全性和疗效。
在纳入的 51 例 SIADH 患者中，39 例患者（16 例女性患者，年龄 70.8±11.3 岁）纳入意向治疗分析。所有患者均接受 15mg/天作为起始剂量，然后根据需要增加至 60mg/天（按需），直至第 4 天。
血清钠在第 1 天至第 24 小时内显著升高（126.8±4.3 与 133.7±3.8mmol/L，P＜0.001），在第 1 天至第 4 天期间逐渐升高（133.7±3.8 与 135.6±3.6mmol/L，P＜0.05），然后在第 11 天达到平台期（136.7±4.5mmol/L）。第 1 天至第 24 小时内血清钠的变化与初始血清钠浓度之间存在显著相关性（r=-0.602，P＜0.001）。在严重低钠血症（＜125mmol/L）患者中，变化幅度显著更高（11.1±4.8mmol/L），而在中度（6.4±2.5mmol/L，P＜0.05）或轻度低钠血症（4.3±3.3mmol/L，P＜0.01）患者中则较低。此外，逻辑回归分析显示，体重（比值比[OR]，0.858；95%置信区间[CI]，0.775-0.976；P=0.020）和体重指数（BMI）（OR，0.692；95%CI，0.500-0.956；P=0.026）与快速纠正相关。未报告严重不良事件，但有 13%的患者出现低钠血症纠正过度。
TLV 可有效纠正低钠血症，在韩国 SIADH 患者中具有良好的耐受性。然而，体重低、BMI 低或严重低钠血症的患者可能对 15mg TLV 的初始剂量易发生过度纠正。
