Diuretic effect and pharmacokinetics of tizolemide in subjects with normal and decreased renal function

Tizolemide, a new sulphonamide diuretic, has alkaline properties and is cleared by a tubular transport system which differs from the PAH-excreting system which transports thiazide diuretics. The effect of this drug on the excretion of sodium and Other electrolytes, and its pharmacokinetics, were evaluated in 5 healthy volunteers and in 10 patients with renal disease who had GFRs ranging from 5-98 ml/min. The saluretic effect of tizolemide was compared with that of placebo. The increase in sodium and chloride excretion after a single dose of 50 mg i.v. was clearly dependent on residual renal function but could be observed in all except one patient. It remains to be assessed whether a full diuretic effect can be achieved in patients with renal insufficiency if higher doses are used. The plasma half-life was 3.0 hours in healthy subjects but increased in patients with renal insufficiency to a maximum of 52 hours. In normal subjects total plasma clearance (611 ml/min) mainly depended on the renal clearance (564 ml/min) which decreased in proportion to GFR, whereas non-renal clearance remained unchanged. The large apparent volume of distribution of the drug (166 l/1.73 m2 BSA) did not increase significantly in uremia. Clinical trials with this drug in patients with reduced renal function must take into account the expected prolongation of its half-life.