Identification of factors affecting meropenem pharmacokinetics in critically ill patients: Impact of inflammation on clearance |
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| Affiliation: | 1. Division of Pharmacy, Chiba University Hospital, Chiba, Japan;2. Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan;3. Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chiba, Japan;1. Division of Bacteriology, Chiba Prefectural Institute of Public Health, 666-2, Nitona, Chuo, Chiba, 260-8715, Japan;2. Center for Emergency Preparedness and Response, National Institute of Infectious Diseases, 4-7-1, Gakuen, Musashi-murayama, Tokyo, 208-0011, Japan;1. Department of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan;2. Department of Infectious Diseases, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan;3. Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan;1. Department of General Internal Medicine, Tenri Hospital, Tenri, Japan;2. Department of Gastrointestinal Surgery, Tenri Hospital, Tenri, Japan;3. Corporate office, Tenri Hospital, Tenri, Japan;1. Department of Pediatrics and Child Health, Nihon University School of Medicine, 30-1 Oyaguchikamicho, Itabashi-ku, Tokyo, 173-8610, Japan;2. Department of Obstetrics and Gynecology, Nihon University School of Medicine, 30-1 Oyaguchikamicho, Itabashi-ku, Tokyo, 173-8610, Japan;3. Department of Neonatology, Hyogo Prefectural Kobe Children''s Hospital, 1-6-7, Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan;4. Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan;5. Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan;6. Center for Recurrent Pregnancy Loss, Teine Keijinkai Hospital, 1-40, Maeda 1-jho, 12-chome, Teine-ku, Sapporo, 006-8555, Japan;7. Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, 3-1, Yamadaoka, Suita, Osaka, 565-0871, Japan;1. Department of Urology, Sapporo Medical University School of Medicine, Japan;2. Department of Infection Control and Laboratory Medicine, Sapporo Medical University School of Medicine, Japan;3. Nagae Prostate Clinic, Japan;4. IClinic, Japan;5. Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan;6. Department of Urology, Dokkyo Medical University, Japan;7. Department of Urology, University of Occupational and Environmental Health, Japan;8. Department of Urology, Kyowakai Medical Corporation Kyoritsu Hospital, Japan;9. Department of Urology, Kobe University Graduate School of Medicine, Japan;10. Department of Urology, Hakodate National Hospital, Japan;1. Department of Microbiology, Fujita Health University School of Medicine, Aichi, Japan;2. Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Aichi, Japan;3. Department of Bacteriology, Nagoya University Graduate School of Medicine, Aichi, Japan;4. Department of Medical Sciences, Shinshu University Graduate School of Medicine, Science and Technology, Nagano, Japan;5. Department of Infectious Diseases, Fujita Health University School of Medicine, Aichi, Japan;6. Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA |
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| Abstract: | IntroductionThe purpose of this study was to explore factors influencing meropenem pharmacokinetics (PKs) in critically ill patients by developing a population PK model and to determine the optimal dosing strategy.MethodsThis prospective observational study involved 12 critically ill patients admitted to the intensive care unit and treated with meropenem 1 g infused over 1 h every 8 h. Blood samples were collected on days 1, 2, and 5 immediately prior to dosing, and at 1, 2, 4, and 6 h after the start of infusion. Population PK parameters were estimated using nonlinear mixed-effects model software.ResultsMeropenem PK was adequately described using a two-compartment model. Typical values of total and inter-compartmental clearance were 9.30 L/h and 9.70 L/h, respectively, and the central and peripheral compartment volumes of distribution were 12.61 L and 7.80 L, respectively. C-reactive protein (CRP) was identified as significant covariate affecting total meropenem clearance. The probability of target attainment (PTA) predicted by Monte Carlo simulations varied according to the patients’ CRP. The PTA of 100% time above the minimum inhibitory concentration ≤2 mg/L for bacteria was achieved after a dose of 1 and 2 g infused over 4 h every 8 h in patients with CRP of 30 and 5 mg/dL, respectively.ConclusionThe findings of this study suggest that CRP might be helpful in managing meropenem dosing in critically ill patients. Higher doses and extended infusion may be required to achieve optimal pharmacodynamic targets. |
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| Keywords: | Meropenem Population pharmacokinetics Critically ill patient |
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