THE PHARMACOKINETICS OF MEROPENEM IN SURGICAL PATIENTS WITH MODERATE OR SEVERE INFECTIONS

The pharmacokinetics of meropenem were studied in a group of 11 surgical patients (four male, seven female; mean age 63 years; mean weight 72 kg) all of whom had moderate or severe infection and who received a mean dose of 14 . 5 mg/kg +/- 2 . 7 meropenem 8-hourly iv for a minimum of 4 days. Venous blood samples were collected at timed intervals after the first dose on day 1 and the second dose on the fourth or fifth day of therapy. Serum meropenem concentrations were assayed by HPLC and fitted to a two compartment pharmacokinetic model. The mean pharmacokinetic parameters (standard deviation) on day 1 were T-1/2 84 . 6 +/- 24 . 1 min, V-dss 0 . 22 +/- 0 . 06 L/kg, AUC 6028 +/- 1983 . 2 mg.min/L, Cl-tot 188 +/- 67 mL/min and MRT 89 . 1 +/- 67 . 8 min. On the fourth or fifth days of therapy the values were T-1/2 79 . 9 +/- 18 . 2 min, V-dss 0 . 17 +/- 0 . 8 L/kg, AUC 6000 . 7 +/- 2417 mg.min/L, Cl-tot 190 +/- 60 mL/min and MRT 67 . 8 +/- 30 . 4 min. Although the T-1/2, V-dss and MRT decreased from day 1 to day 4 or 5 these changes were not statistically significant (Student's t-test, P > 0 . 05). Total clearance of meropenem was linearly related to creatinine clearance or patient age on the first day of therapy. Although the T-1/2 and MRT were longer and the Cl-tot lower than those reported for young healthy volunteers, they were similar to those found in elderly volunteers. As the pharmacokinetic parameters remained constant over the duration of therapy rather than being related to severity of infection or surgery we conclude that dosage modification of meropenem is not required for patients with moderate or severe infection.