Kinetic interactions between azlocillin, cefotaxime, and cefotaxime metabolites in normal and impaired renal function

Cefotaxime (CTX) kinetics, alone and in combination with azlocillin (AZ), were determined in 18 subjects with either normal or impaired renal function. After the single dose and with increasing renal insufficiency, total CTX clearance fell from 266 to 71 ml/min/1.73 m2. At the same time the terminal t1/2 rose from 1.1 to 2.8 hr. Regardless of the degree of renal function, CTX clearance in combination with AZ in all patients was only 50% to 60% of that with CTX alone. This reduction in total body clearance was due to a parallel decrease in renal and nonrenal clearance. In advanced renal failure, particularly after AZ, the terminal t1/2 of the CTX metabolites increased up to 1000% to 1500% of normal. On the basis of these findings, CTX dosage adjustment is recommended only in patients with a glomerular filtration rate (GFR) below 20 ml/min. After AZ, however, dosage reduction of CTX seems to be advisable at an earlier stage of renal impairment (GFR 40 ml/min).