Elimination of amphotericin B in impaired renal function

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Abstract
Amphotericin B has been an important drug in the treatment of systemic mycoses, although its nephrotoxicity has limited its use in uremic and nonuremic patients. The influence of impaired renal function on the steady-state plasma clearance of amphotericin B was determined in 7 patients with creatinine clearances ranging from zero to normal. Contrary to previous reports, steady-state plasma concentrations of total drug were lower in uremic patients than in patients with normal and renal function. Total plasma clearance of amphotericin B ranged from 16.7-39.9 ml/min, correlated directly with the plasma creatinine concentration and correlated inversely with the creatinine clearance. Urinary excretion of unchanged drug accounted for less than 10% of the dose. In 10 healthy subjects, mean percent of amphotericin B unbound in plasma was 3.55 .+-. 0.32 (SD). Binding was determined in a further group of 10 uremic patients. Mean unbound percent (4.15 .+-. 0.73, SD) was higher than in the healthy subjects, and the binding ratio (molar concentration of bound to unbound drug) correlated weakly with the creatinine clearance. Plasma clearance of unbound amphotericin B and, therefore, steady-state plasma concentrations of unbound drug are apparently not affected by renal impairment, and dosage requirements will be overestimated if based on measurements of total drug plasma concentration.

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