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内容記述 |
Infants and young children are prone to hyperkalemia caused by decreased renal potassium excretion. However, there are limitations to the use of current hyperkalemia drugs in pediatric patients. To address this issue, we developed a young rat hyperkalemia model by the combined administration of potassium chloride (KCl) and amiloride (Ami) to test new drug candidates for young patients. We administered KCl (2, 3, 4.5, and 6 mEq/kg) and Ami (3 mg/kg) intraperitoneally to five-week-old male Wistar-Imamichi rats and placed them in metabolic cages. After 6 h, blood and urine samples were collected. The combined administration of KCl and Ami increased the serum-potassium concentration compared to the control (2 mEq/kg; 5.2 vs 4.5 mEq/L, P = 0.039, 6 mEq/kg; 6.8 vs 4.1 mEq/L, P = 0.005, n = 5) in a dose-dependent manner. Next, the rats were orally administered furosemide (30 mg/kg, FURO), a known hyperkalemia treatment, or Compound 21 (C21) (10 and 30 mg/kg), an angiotensin II type 2 receptor agonist and candidate drug for hyperkalemia. FURO was administered as a single dose (after 1 h) or as repeated doses (after 1, 3, and 5 h). The serum-potassium concentration was significantly decreased by FURO (single dose; 5.9 vs 6.8 mEq/L, P = 0.017, n = 7, repeated doses; 5.6 vs 6.3 mEq/L, P = 0.021, n = 7). However, C21 did not decrease the serum-potassium concentration compared to the control (6.6 vs 6.8 vs 7.2 mEq/L, P = 0.07). Overall, this model can be used to evaluate the effects of candidate therapeutic drugs for hyperkalemia in school children caused by decreased urinary-potassium excretion. |