STEADY-STATE PHARMACOKINETICS OF CEFOPERAZONE AND SULBACTAM IN PATIENTS WITH ACUTE APPENDICITIS

OBJECTIVE: To determine the steady-state pharmacokinetics of intraveno usly administered cefoperazone and sulbactam when given in combination to patients with acute appendicitis. METHODS: Six patients with norma l renal and hepatic function received cefoperazone 2 g with sulbactam 1 g prior to appendectomy and then every 12 hours. Serial blood sample s were collected after each patient received at least three doses of c efoperazone/sulbactam. RESULTS: Cefoperazone and sulbactam could be be st described by a two-compartment model. Mean +/- SD values for cefope razone steady-state volume of distribution (V(d)ss)), elimination half -life (t1/2beta), clearance (Cl), and area under the curve (AUC0-t) we re 19.8 +/- 8.0 L, 3.97 +/- 1.06 h, 62.6 +/- 16.3 mL/min, and 556.9 +/ - 122.0 mg.h/L, respectively. Sulbactam V(d)ss, t1/2beta, Cl, and AUC0 -t were 34.7 +/- 13.9 L, 1.39 +/- 0.4 h, 288.6 +/- 68.2 mL/min, and 64 .8 +/- 24.5 mg.h/L, respectively. CONCLUSIONS: Compared with data from healthy volunteers, cefoperazone exhibited a decreased Cl and increas ed V(d)ss and t1/2beta in patients with acute appendicitis. An increas ed V(d)ss also was observed for sulbactam. The disposition of cefopera zone/sulbactam is altered in this group of patients; however, these ch anges are not likely to warrant a dosage reduction.