Pharmacokinetics of metolazone in normal subjects and in patients with cardiac or renal failure.

Abstract

The pharmacokinetics of metolazane (Zaroxolyn) have been studied in normal adult volunteers after oral or intravenous administration and after oral administration in patients requiring diuretic therapy fOT severe renal failure, fOT moderate renal failure, and for heart disease. Following intravenous administration in normal subjects, plasma concentration fell in a bi‐exponential fashion. The data were fitted to the two‐compartment open model and the appropriate kinetic parameters were calculated. The drug was faund to be extensively distributed in the tissue compartment, anly one third of the body cantent after equilibrium being in the plasma compartment. The elimination rate constant was 0.13 hr‐1. Clearance of metolazone from the central compartment was approximately equal to creatinine clearance and ranged from 110 ml per minute in normal subjects to 20 ml per minute in severe renal failure. Absorption was 64% in normal controls, hut as little as 40% of the oral dose was ahsorbed in some patients. Abaut 95% of plasma metolazone was bound to plasma pro teins in normal controls. This figure fell to 90% in severe renal failure. About 10% of the dose was excreted in bile by normal subjects.