Pharmacokinetics of Meropenem Determined by Microdialysis in the Peritoneal Fluid of Patients With Severe Peritonitis Associated With Septic Shock

Abstract

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.

Population Pharmacokinetics and Target Attainment of Meropenem in Plasma and Tissue of Morbidly Obese Patients after Laparoscopic Intraperitoneal Surgery

“…The penetration of meropenem into peritoneal fluid was rapid, the exposures were roughly comparable to those in plasma, and the between-patient variability of F PF was relatively small (Table 2). The estimated extent of penetration into peritoneal fluid (F PF ) in our study was in good agreement with previously reported estimates that ranged from 0.74 to 1.0 (32,33).…”

“…2; Table 2). Previous studies on the penetration of meropenem into subcutaneous tissue and peritoneal fluid showed rapid equilibration after the end of the infusion (31,33). Our sampling times ensured that we could adequately characterize the terminal phase and, therefore, the fT ϾMIC .…”

An Open, Randomized, Single-Center, Crossover Pharmacokinetic Study of Meropenem after Intraperitoneal and Intravenous Administration in Patients Receiving Automated Peritoneal Dialysis

“…via a microdialysis technique. Meropenem areas under the concentration-time curve in peritoneal fluid reached 73.8% (SD, Ϯ15%) of plasma levels and were thus only slightly lower than in the blood (16). Of interest, the degradation of meropenem ex vivo in the peritoneal fluid was also demonstrated.…”

Metronidazole and Hydroxymetronidazole Central Nervous System Distribution: 1. Microdialysis Assessment of Brain Extracellular Fluid Concentrations in Patients with Acute Brain Injury

“…The in vivo relative recovery by loss was calculated for each dialysate collected, and the mean value was used to correct the dialysate concentrations (19). The metronidazole residual unbound concentration in brain was taken into consideration to estimate recovery, as previously described (20). Briefly, in vivo recovery was calculated for each interval as presented in the following equation: in vivo recovery ϭ [(C in ϩ C ext ) Ϫ C out ]/C in , where C in and C out are the perfusate and dialysate metronidazole concentrations and C ext is the extrapolated concentration of metronidazole in the dialysate at the midpoint of the retrodialysis interval of collection.…”