Two groups of 10 healthy ambulatory subjects, i.e., a group of 10 persons s30 years of age (mean age, 27.6 years) and a group of 10 persons .65 years of age (mean age, 70 years), were randomized in a single-trial crossover design to receive 1 and 2 g of cefoperazone with a 1-week washout between doses. The elderly subjects had both decreased estimated creatinine clearances and decreased albumin concentrations in serum. Cefoperazone concentrations in serum of elderly persons were significantly higher at each interval from 30 min to 6 h for the 2-g dose. Compared with that in younger persons, the total clearance in elderly subjects was significantly lower for both the 1-and 2-g doses, the renal clearance was significantly lower for the 2-g dose, and the area under the curve was significantly higher for the 2-g dose in the elderly persons. The half-life at i phase was higher in the elderly persons at both the 1-and 2-g doses but not significantly so. Changes in total clearance and area under the curve and higher levels in serum in the elderly persons suggest a longer duration of antimicrobial activity in this age group.The elderly (persons of >65 years of age) represent a significant and growing portion of the U.S. population, making up 12% of the total population in 1980 and estimated to increase to 17% in the year 2030 (38). Disproportionate percentages of health care expenditures (25 to 30%) (22) and prescription drugs dispensed (25%) (9) are generated by this segment of the population. In addition, the incidence of adverse reactions to drugs has been clearly demonstrated to be greater in the elderly (18).The newer extended-spectrum beta-lactam antimicrobial agents, with their potent antibacterial activity and relative lack of toxicity, are finding increased use as preferred agents for the treatment of elderly patients with infection. Their safety profile appears to be greater than that of the aminoglycosides that have been shown to be associated with increased rates of toxicity in the elderly (27).In view of age-associated altered drug absorption and disposition, decreased protein binding, renal clearance, hepatic drug metabolism (30, 33), and albumin levels (5, 26), and increased drug-drug interactions, it is possible that the pharmacokinetics of the new beta-lactam agents are altered as well. The pharmacokinetic properties of ceftriaxone (25), ceftazidime (23), and cefotaxime (20) in the elderly have shown differences compared with those in younger subjects.The pharmacokinetic properties of cefoperazone, a broadspectrum antipseudomonal cephalosporin (19), have been studied in healthy young volunteers. Excretion is via dual pathways; 15 to 37% is excreted in urine, with the remainder excreted by nonrenal mechanisms, predominantly the hepatobiliary system (12,17,36). Additional studies have been done in patients with impaired renal and hepatic functions (2,7,8,17) and in patients with renal dysfunction and active infection (32); altered pharmacokinetic parameters have been noted in these studies. We report here...