ISEPAMICIN DISPOSITION IN SUBJECTS WITH VARIOUS DEGREES OF RENAL-FUNCTION

The disposition of isepamicin, an ivestigational aminoglycoside antibiotic, was evaluated in 30 subjects with various degrees of renal function. The subjects were divided into five groups: those with normal renal function (creatinine clearance [CL(CR)], > 80 ml/min/1.73 m2), those with mild renal insufficiency (CL(CR), 50 to 80 ml/min/1.73 m2), those with moderate renal insufficiency (CL(CR), 30 to 49 ml/min/1.73 m2), those with severe renal insufficiency (CL(CR), 5 to 29 ml/min/1.73 m2), and those maintained on hemodialysis (CL(CR), < 5 ml/min/1.73 m2). Subjects on hemodialysis were studied both during hemodialysis and during an interdialytic period. The volumes of distribution of isepamicin were not significantly different among the five groups of patients. The total body clearance (CL(P)) and renal clearance (CL(R)) of isepamicin significantly decreased as CL(CR) decreased. The CL(P) of isepamicin and CL(CR) were significantly related {(CL(P) = 0.391 . [CL(CR)] + 1.83; r2 = 0.878)}. Nonrenal clearance of isepamicin did not differ between groups. Hemodialysis augmented the CL(P) of isepamicin by approximately 25-fold. The amount of isepamicin recovered in the dialysate was 60.6 +/- 15.8% of the dose administered. The maximal rebound of the isepamicin concentration in plasma after cessation of hemodialysis was observed at 0.78 +/- 0.7 h. Concentrations in plasma increased 32.7 +/- 22.9% over that measured at the end of hemodialysis. These data indicate that dosage adjustments are necessary in subjects with decreased renal function.