Pharmacokinetics of cefoperazone (2.0 g) and sulbactam (1.0 g) coadministered to subjects with normal renal function, patients with decreased renal function, and patients with end-stage renal disease on hemodialysis

Publisher Website
Google Scholar
Abstract
The singe-dose pharmacokinetics of intravenously administered cefoperazone (2.0 g) and sulbactam (1.0 g) were studied in normal sujects and in patients with various degrees of renal failure. In an open, parallel experimental design, six normal subjects (creatinine, clearance, greater than 90 ml/min), two patients with mild renal failure (creatinine clearance, 31 to 60 ml/min), eight patients with moderate renal failure (creatinine clearance, 7 to 30 ml/min), and four functionally anephric patients (creatinine clearance, less than 7 ml/min) were studied. The functionally anephric patients were given two test doses to allow study of drug disposition both on and off hemodialysis. Serial blood and urine samples were collected from time zero to 12 h after dosing in normal subjects and from 0 to 72 h in renal patients. Serum concentrations of both drugs declined biexponentially. For cefoperazone, the terminal elimination half-lives averaged from 1.6 to 3.0 h and were similar in subjects and patients. No cefoperazone pharmacokinetic parameters were appreciably altered by renal failure or hemodialysis, and thre was no correlation between the total boy clearance of cefoperazone and estimated creatinine clearance. In contrast, the sulbactam total body clearance was highly correlated with estimated creatinine clearance (r = 0.92, P < 0.01) and was significantly higher in normal volunteers than in the renally impaired groups (P < 0.01). The sulbactam terminal elimination half-life in functionally anephric patients (9.7 .+-. 5.3 h ) differed significantly from that of normal volunteers (1.0 .+-. 0.2 h) and patients with mild renal failure (1.7 .+-. 0.7 h, P < 0.05). The sulbactam half-life in moderate renal failure was 4.6 .+-. 2.2 h. The hemodialysis extraction ratio of sulbactam (0.44) was significantly higher than that of cefoperazone (0.05) (P < 0.01). The mean percentage of the dose recovered from dialysate was about 4% for cefoperazone and 30% for sulbactam. Hemodialysis patients showed a significantly higher sulbactam apparent volume of distribution at steady state and total body clearance during dialysis periods when compared with those in periods off dialysis. The sulbactam elimination half-life was appreciably altered during the hemodialysis period (mean, 2.0 h). Hemodialysis approximately doubled the sulbactam total body clearance. When cefoperazone and sulbactam are used in combination, adjustment of the dosing regimen for patients with estimated creatinine clearance of less than 30 ml/min can be made to compensate for reduced sulbactam total body clearance. An adjustment may be particularly appropriate at an estimated creatinine clearance of less than 15 ml/min. Under these conditions, the combination may be given once daily, with an additional dose of cefoperazone (given alone) 12 h later. This alternating regimen would not require further adjustment after hemodialysis treatment, but we recommend that dosing the scheduled to follow hemodialysis if possible.