Diuretic induced hypokalaemia: relationship to dosage interval and plasma aldosterone

Plasma potassium and aldosterone responses to 9 days treatment with hydrochlorothiazide (100 mg/day) alone or in combination with spironolactone (100 mg/day), prescribed once daily or in doses 12 h apart, were examined in a double-blind, crossover study in twelve healthy subjects. Plasma potassium concentrations were lower when the drugs were administered 12 h apart (P less than 0.01). Spironolactone attenuated significantly hydrochlorothiazide induced hypokalaemia--mean rise in plasma potassium, 0.36 mmol/l (P less than 0.001). The increase in plasma aldosterone was greater following combination therapies (P less than 0.001), but there were no significant differences between once daily and twice daily regimens. We conclude that plasma potassium concentration is better maintained when diuretics are given once daily and that this is not related closely to differences in plasma aldosterone responses.