Pharmacokinetic properties of mezlocillin in ambulatory elderly subjects

Twelve healthy ambulatory elderly subjects (mean age, 73-78 years) randomly received either a 4-g or 5-g dose of mezlocillin intravenously. One week later the regimen was repeated and patients crossed over to the other dose. Peak serum concentrations were 165 mg/L and 281 mg/L for the 4-g and 5-g doses, respectively. For both doses, differences in t(1/2β) (1.32 hr vs 1.13 hr), AUC (275 mg·hr/L vs 403 mg·hr/L), CL (207 mL/min vs 174 mL/min), CL(R) (59 mL/min vs 45 mL/min), CL(NR) (152 mL/min vs 130 mL/min) were not statistically significant. The differences in V(area) (22.4L vs 168.8L, P ≤ .01) and C(max) (216.6 mg/L vs 317 mg/L, P ≤ .05) were statistically significant. Comparison with pharmacokinetic parameters obtained in younger subjects following the 5-g dose reveals that in the elderly the AUC, V(area), and CL(NR) are higher whereas the CL and CL(R) are lower. The elderly demonstrated an increase in nonrenal clearance compared with young subjects that is not fully compensatory. The increased AUC in the elderly group suggests that clinical studies examining mezlocillin doses and dose intervals in the treatment of serious infections are warranted in infected elderly patients.