Age and ceftriaxone kinetics.

One gram ceftriaxone was injected at a constant rate in an intravenous infusion over 30 min to eight elderly subjects (mean age, 70.5 yr) and eight young subjects (mean age, 28.9 yr); the latter served as body weight-matched controls. Plasma and urine samples were collected in serial order for 48 hr and assayed for unchanged drug. Selected plasma samples were subjected to protein binding determinations by equilibrium dialysis. Statistical comparison of data for the old and young indicated no significant changes in means of (1) maximum plasma concentration (140 and 133 micrograms/ml); (2) elimination rate constant (0.078 and 0.093 hr-1) and elimination t1/2 (8.9 and 7.5 hr); (3) apparent volume of distribution (10.69 and 11.01 l); (4) plasma clearance (833 and 1023 ml/hr); (5) nonrenal clearance (515 and 606 ml/hr); and (6) percent dose excreted unchanged in urine (39.6 and 41.4). There was, however, a significant decrease in the renal clearance (318 and 416 ml/hr) and a significant increase in the plasma free fractions (0.157 and 0.136 at 100 micrograms/ml and 0.146 and 0.114 at 60 to 70 micrograms/ml) of ceftriaxone in elderly subjects. The 24% decrease in renal clearance in the elderly subjects corresponded to the 19% decrease in their creatinine clearance. Since the age-related changes in kinetics were relatively small, it is concluded that dosage adjustment is probably not necessary for elderly subjects requiring ceftriaxone.