Pharmacokinetics of Prophylactic Ampicillin–Sulbactam and Dosing Optimization in Patients Undergoing Cardiovascular Surgery with Cardiopulmonary Bypass
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- Yokoyama Yuta
- Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University Department of Clinical Pharmacotherapy, Hiroshima University
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- Matsumoto Kazuaki
- Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University
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- Ikawa Kazuro
- Department of Clinical Pharmacotherapy, Hiroshima University
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- Watanabe Erika
- Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University
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- Yamamoto Hiroyuki
- Department of Thoracic, Cardiovascular and Hepato-Biliary-Pancreatic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University
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- Imoto Yutaka
- Department of Thoracic, Cardiovascular and Hepato-Biliary-Pancreatic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University
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- Morikawa Norifumi
- Department of Clinical Pharmacotherapy, Hiroshima University
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- Takeda Yasuo
- Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University
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Abstract
Antibiotic concentrations must be maintained at an adequate level throughout cardiovascular surgery to prevent surgical site infection. This study aimed to determine the most appropriate timing for intraoperative repeated dosing of ampicillin–sulbactam, a commonly used antibiotic prophylaxis regimen, to maintain adequate concentrations throughout the course of cardiovascular surgery with cardiopulmonary bypass (CPB). The total plasma concentrations of ampicillin were monitored in 8 patients after ampicillin (1 g)–sulbactam (0.5 g) administration via initial intravenous infusion and subsequent CPB priming. Pharmacokinetic parameters were estimated and used to predict the free plasma concentrations of ampicillin. The mean values for the volume of distribution, elimination rate constant, elimination half-life, and total clearance of ampicillin were 15.8±4.1 L, 0.505±0.186 h−1, 1.52±0.47 h, and 7.72±2.72 L/h, respectively. When ampicillin (1 g)–sulbactam (0.5 g) was intravenously administered every 3, 4, 6, and 12 h after the start of CPB, the predicted free trough plasma concentrations of ampicillin were 15.20, 8.25, 2.74, and 0.13 µg/mL, respectively. Therefore, an every-6-h regimen was needed to maintain the free ampicillin concentration at more than 2 µg/mL during cardiovascular surgery with CPB. We suggest that the dose and dosing interval for ampicillin–sulbactam should be adjusted to optimize the efficacy and safety of treatment, according to the minimum inhibitory concentrations for methicillin-sensitive Staphylococcus aureus isolates at each institution. Registration number: UMIN000007356.
Journal
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- Biological and Pharmaceutical Bulletin
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Biological and Pharmaceutical Bulletin 38 (11), 1817-1821, 2015
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390282679608598528
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- NII Article ID
- 130005106382
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- NII Book ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL BIB ID
- 026830559
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- PubMed
- 26521833
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- Text Lang
- en
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- Data Source
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- JaLC
- IRDB
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
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- Abstract License Flag
- Disallowed