Chlorthalidone – a renaissance in use?

Diuretic therapy remains a mainstay of hypertension treatment, either given as monotherapy or used in combination with other antihypertensive compounds. Several issues have complicated the issue of diuretic use with that of class effect being the one that has proven most difficult. Hydrochlorothiazide is a commonly used thiazide diuretic; whereas chlorthalidone is a structurally similar compound, quite dissimilar pharmacokinetically with a much longer half-life for effect and a wider volume of distribution with heavy partitioning in red blood cells. These pharmacokinetic features afford chlorthalidone a unique advantage in its capacity to act as an effective diuretic and blood-pressure-lowering agent, as well as a compound that improves cardiovascular outcomes in the patient with hypertension. Chlorthalidone has been used sparingly in clinical practice in large measure because it is not readily available in many fixed-dose combination products. Fixed-dose combinations containing chlorthalidone and an angiotensin-receptor blocker are now in development. It remains to be determined how well these two therapies will reduce blood pressure in the general population while keeping compound-specific side effects to a minimum.