Pharmacokinetic evaluation of meropenem and imipenem in critically ill patients with sepsis

Objective: To evaluate and compare the pharmacokinetic profiles of imipenem and meropenem in a population of critically ill patients with sepsis to find possible differences that may help in selecting the most appropriate drug and/or dosage in order to optimise empiric antimicrobial therapy. Patients and methods: This was a single-centre, randomised, nonblind study of the pharmacokinetics of both intravenous imipenem 1g and meropenem 1 g in 20 patients admitted to an intensive care unit with sepsis in whom antimicrobial therapy was indicated on clinical grounds. Patients were divided into two groups: group I received intravenous imipenem 1g plus cilastatin 1g, and group II received intravenous meropenem 1g over 30 minutes. Peripheral blood samples were collected at 0, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4, 6 and 8 hours after the first dose and were centrifuged for 10 minutes at 4 degrees C. Urine samples were collected during the 8 hours after antimicrobial administration at 2-hour intervals: 0-2, 2-4, 4-6 and 6-8 hours. The total volume of urine was recorded; the serum and urine samples were immediately frozen and stored at -80 degrees C until assayed. Pharmacokinetic analysis was carried out through computerised programs using the least-square regression method and a two-compartment open model. Statistical differences were evaluated by means of one-way ANOVA. Results: The following pharmacokinetic differences between the two drugs were observed: the imipenem mean peak serum concentration was significantly higher than for meropenem (90.1 +/- 50.9 vs 46.6 +/- 14.6 mg/L, p < 0.01); the area under the serum concentration-time curve was significantly higher for imipenem than for meropenem (216.5 +/- 86.3 vs 99.5 +/- 23.9 mg center dot h/L, p < 0.01), while the mean volume of distribution and mean total clearance were significantly higher for meropenem than for imipenem (25 +/- 4.1 vs 17.4 +/- 4.5L, p < 0.01 and 191 +/- 52.2 vs 116.4 +/- 42.3 mL/min, p < 0.01, respectively). Conclusion: The more favourable pharmacokinetic profile of imipenem compared with meropenem in critically ill patients with sepsis might balance the possibly greater potency demonstrated in vitro for meropenem against Gram-negative strains. Hence, the clinical efficacy of the two carbapenems depends mostly on their correct dosage.