Effect of Age and Renal Function on the Pharmacokinetics of Coadministered Cefoperazone and Sulbactam

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The single dose pharmacokinetics of cefoperazone 1g and sulbactam 0.5g, coadministered intravenously, were evaluated in 3 different age groups. Eight healthy young, 8 healthy middleaged, and 8 healthy elderly adults were studied in an open design. The terminal half-life of cefoperazone (3.0 vs 2.3 hours) was 1.3 times greater in the elderly than in the young subjects and 2.5 times greater for sulbactam (1.8 vs 0.7 hours). Total sulbactam clearance was found to correlate better with age (r = 0.59) than was total cefoperazone clearance (r = 0.40). Volume of distribution, adjusted for bodyweight, remained constant with age. The relationship between creatinine clearance (CLCR) and age in this study is described as (CLCR = -1.37 age + 158.28; r = 0.72, p = 0.0001). Multivariate regression analysis of total body clearance versus age and creatinine clearance did not significantly improve the correlation for sulbactam (r = 0.62, p = 0.95) or cefoperazone (r = 0.44, p = 0.87). Sulbactam remained at or above the serum concentrations (8 mg/L) considered to provide optimal synergy with cefoperazone for 1.8, 2.2 and 3.3 hours postinfusion in the young, middle-aged and elderly subjects, respectively.

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