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 T1/2 84.6 +/- 24.1 min, Vdss 0.22 +/- 0.06 L/kg, AUC 6028 +/- 1983.2 mg.min/L, Cltot 188 +/- 67 mL/min and MRT 89.1 +/- 67.8 min. On the fourth or fifth days of therapy the values were T1/2 79.9 +/- 18.2 min, Vdss 0.17 +/- 0.8 L/kg, AUC 6000.7 +/- 2417 mg.min/L, Cltot 190 +/- 60 mL/min and MRT 67.8 +/- 30.4 min. Although the T1/2, Vdss 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 T1/2 and MRT were longer and the Cltot lower than those reported for young healthy volunteers, they were similar to those found in elderly volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)
Lovering
A M
AM
Department of Medical Microbiology, Southmead Health Services NHS Trust, Westbury-on-Trym, Bristol, UK.
Vickery
C J
CJ
Watkin
D S
DS
Leaper
D
D
McMullin
C M
CM
White
L O
LO
Reeves
D S
DS
MacGowan
A P
AP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001424:Bacterial Infections / Q000097:blood / Q000378:metabolism* / Q000601:surgery; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D008297:Male; D000077731:Meropenem; D008875:Middle Aged; D008954:Models, Biological; D013056:Spectrophotometry, Ultraviolet; D013514:Surgical Procedures, Operative; D013845:Thienamycins / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
D013845:Thienamycins; D000077731:Meropenem