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.
The single-dose pharmacokinetics of intravenously administered cefoperazone (2.0 g) and sulbactam (1.0 g) were studied in normal subjects 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 there was no correlation between the total body 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 less than 0.01) and was significantly higher in normal volunteers than in the renally impaired groups (P less than 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 less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Reitberg
D P
DP
Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo.
Marble
D A
DA
Schultz
R W
RW
Whall
T J
TJ
Schentag
J J
JJ
D000328:Adult; D000368:Aged; D002438:Cefoperazone / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007674:Kidney Diseases / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D013407:Sulbactam / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
D002438:Cefoperazone; D013407:Sulbactam