Pharmacokinetics of Prophylactic Ampicillin–Sulbactam and Dosing Optimization in Patients Undergoing Cardiovascular Surgery with Cardiopulmonary Bypass

• Yokoyama Yuta

  Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University Department of Clinical Pharmacotherapy, Hiroshima University

• Matsumoto Kazuaki

  Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University

• Ikawa Kazuro

  Department of Clinical Pharmacotherapy, Hiroshima University

• Watanabe Erika

  Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University

• Yamamoto Hiroyuki

  Department of Thoracic, Cardiovascular and Hepato-Biliary-Pancreatic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University

• Imoto Yutaka

  Department of Thoracic, Cardiovascular and Hepato-Biliary-Pancreatic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University

• Morikawa Norifumi

  Department of Clinical Pharmacotherapy, Hiroshima University

• Takeda Yasuo

  Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University

抄録

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.

収録刊行物

• Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ

  Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ 38 (11), 1817-1821, 2015

  公益社団法人 日本薬学会

キーワード

• ampicillin
• sulbactam
• cardiovascular surgery
• prophylaxis
• cardiopulmonary bypass

詳細情報

• CRID: 1390282679608598528
• NII論文ID: 130005106382
• NII書誌ID: AA10885497
• DOI: 10.1248/bpb.b15-00334
• ISSN: 13475215
• ISSN: 09186158
• NDL書誌ID: 026830559
• PubMed: 26521833
• Web Site: http://ir.lib.hiroshima-u.ac.jp/00046714
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I026830559
• Web Site: https://www.jstage.jst.go.jp/article/bpb/38/11/38_b15-00334/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2016201574
• 本文言語コード: en
• データソース種別:
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  • IRDB
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• 抄録ライセンスフラグ: 使用不可