A double-blind crossover comparison was made in 18 nonedematous hypertensive subjects with glomerular filtration rates exceeding 70 ml/min/1.73 m2 of the effects of 5 mg metolazone and 5 mg bendroflumethiazide on blood pressure and metabolic parameters. After a 4-wk run-in placebo period, patients received either metolazone or bendroflumethiazide for 6 wk in a crossover fashion with an intervening washout period of 4 wk. Metolazone induced a more sustained and greater blood pressure response than bendroflumethiazide. Changes in plasma potassium, urate, bicarbonate, renin, and angiotensin II occurred during treatment with both metolazone and bendroflumethiazide; the only significant difference, however, was in changes in plasma bicarbonate. Total body potassium (TBK), measured by whole-body monitor, did not fall outside the normal range with either metolazone or bendroflumethiazide, although metolazone induced a greater reduction in TBK (6.2 gm, 5.5% of TBK) than bendroflumethiazide (1.2 gm, 1.1% of TBK, p < 0.05). Our results suggest that metolazone is a more effective antihypertensive and induces similar but greater metabolic changes than bendroflumethiazide. The results of our comparison suggest that although changes in plasma potassium and TBK are minor, they are greater with metolazone, and potassium supplements may not be necessary in nonedematous hypertensive patients with normal renal function.

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