Mezlocillin Pharmacokinetics After Single Intravenous Doses to Patients with Varying Degrees of Renal Function

Abstract

The pharmacokinetics of mezlocillin were examined after single 2- and 4-g intravenous injections to three groups of male patients with creatinine clearances of I ≥ 60, II = 21 to 59, and III ≤ 20 ml min −1 1.73 m −2 . The decline in serum antibiotic levels was biphasic in all groups, and serum data were interpreted in terms of the pharmacokinetic two-compartment model. The mean elimination half-life of mezlocillin after the 2-g dose was 1.3, 1.5, and 2.3 h in groups I, II, and III, respectively. Equivalent values after the 4-g dose were 1.2, 1.6, and 4.4 h. In three functionally anephric patients the mean serum half-life of mezlocillin was 1.5 h during hemodialysis. Mean antibiotic levels in serum were greater than 10 μg ml −1 for 4 h after the 2- and 4-g doses in group I and 8 h in group II. In group III, levels greater than 10 μg ml −1 were maintained for 6 h after the 2-g dose and over 12 h after the 4-g dose. Mezlocillin distribution characteristics were largely independent of renal function and dose size. The only observable change occurred in the value of V dss , which was significantly increased to 0.32 with 0.38 liter kg −1 in severe renal impairment, compared to ca. 0.2 liter kg −1 in subjects with normal or slightly impaired renal function. Cumulative 24-h urinary excretion accounted for 50, 40, and 3.2% of the dose in groups I, II, and III, respectively. Urine levels of mezlocillin were uniformly greater than the minimum inhibitory concentration for susceptible organisms for 12 h after dosing in all patients who produced urine. Because of the relatively small increase in the mezlocillin elimination half-life with declining renal function, dose reduction is necessary only in cases of severe renal impairment.