Pharmacokinetics of meropenem determined by microdialysis in the peritoneal fluid of patients with severe peritonitis associated with septic shock.
Our objective was to describe the pharmacokinetics of meropenem in the peritoneal fluid (PF) of six patients with severe peritonitis and septic shock and to relate measured concentrations to the minimum inhibitory concentration of bacteria. Microdialysis catheters were placed into the peritoneal space during surgery. Meropenem concentrations in plasma and in PF were analyzed using compartmental modeling. Meropenem areas under the concentration-time curve were lower in PF than in plasma (average ratio, 73.8+/-15%) because of degradation confirmed ex vivo. Compartment modeling with elimination from a peripheral compartment described the data adequately, and was used to simulate steady-state concentration profiles in plasma and PF during various dosing regimens. At the currently recommended dosing regimen of 1 g infused over 20 min every 8 h, PF concentrations of meropenem in patients with severe peritonitis associated with septic shock reach values sufficient for antibacterial effects against susceptible, but not always against intermediately susceptible, bacteria.
Clinic of Anaesthesiology and Intensive Care, University of Tartu, Tartu, Estonia.
J
J
Karjagin
S
S
Lefeuvre
K
K
Oselin
K
K
Kipper
S
S
Marchand
A
A
Tikkerberi
J
J
Starkopf
W
W
Couet
R J
RJ
Sawchuk
D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001202:Ascitic Fluid / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D005260:Female; D006801:Humans; D008297:Male; D000077731:Meropenem; D017551:Microdialysis / Q000379:methods*; D008875:Middle Aged; D010538:Peritonitis / Q000097:blood* / Q000188:drug therapy / Q000382:microbiology; D012772:Shock, Septic / Q000097:blood* / Q000188:drug therapy / Q000382:microbiology; D013845:Thienamycins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology
D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem