亚胺培南与美罗培南在重症脓毒血症患者中的药代动力学对比

亚胺培南与美罗培南在重症脓毒血症患者中的药代动力学对比以及安全性

ORIGINAL RESEARCH ARTICLEClin Pharmacokinet 2005; 44 (5): 539-5490312-5963/05/0005-0539/$34.95/0

© 2005 Adis Data Information BV. All rights reserved.

Pharmacokinetic Evaluation ofMeropenem and Imipenem inCritically Ill Patients with Sepsis

Andrea Novelli,1 Chiara Adembri,2 Paola Livi,2 Stefania Fallani,1 Teresita Mazzei1 andAngelo Raffaele De Gaudio2

1

2Dipartimento di Farmacologia Preclinica e Clinica ‘Mario Aiazzi Mancini’, Universit`a diFirenze, Firenze, ItalyDipartimento di Area Critica Medico Chirurgica, Sezione di Anestesia e Terapia Intensiva,

Universit`a di Firenze, Firenze, Italy

AbstractObjective: 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 1g 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 4ºC. 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 –80ºC until assayed. Pharmacoki-

netic analysis was carried out through computerised programs using the least-

square regression method and a two-compartment open model. Statistical differ-

ences 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 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 com-

pared with meropenem in critically ill patients with sepsis might balance the

possibly greater potency demonstrated in vitro for meropenem against Gram-