EFFECT OF AGE AND RENAL-FUNCTION ON THE PHARMACOKINETICS OF COADMINISTERED CEFOPERAZONE AND SULBACTAM

The single dose pharmacokinetics of cefoperazone lg and sulbactam 0.5g , coadministered intravenously, were evaluated in 3 different age grou ps. Eight healthy young, 8 healthy middle-aged, and 8 healthy elderly adults were studied in an open design. The terminal half-life of cefop erazone (3.0 vs 2.3 hours) was 1.3 times greater in the elderly than i n the young subjects and 2.5 times greater for sulbactam (1.8 vs 0.7 h ours). Total sulbactam clearance was found to correlate better with ag e (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 (CL(CR)) and age in this study is described as (CL(CR) = -1.37 age + 158.28; r = 0.72, p = 0.0 001). Multivariate regression analysis of total body clearance versus age and creatinine clearance did not significantly improve the correla tion 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 sub jects, respectively.