Population Pharmacokinetic Model and Dosing Simulation of Meropenem Using Measured Creatinine Clearance for Patients with Sepsis

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K08963
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54030:Infectious disease medicine-related
• Research Institution: Showa University
• Principal Investigator: OHBAYASHI MASAYUKI 昭和大学, 薬学部, 准教授 (70349041)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: メロペネム / 敗血症 / 母集団薬物動態モデル / クレアチンクリアランス / 薬物動態

Outline of Final Research Achievements

The construction of a model that could accurately predict meropenem concentrations in patients with sepsis by the accurate assessment of renal function using measured CCr served as the novelty of this study. In addition, the recommended administration regimen that could achieve PTA based on the renal function and pathogen's MIC was demonstrated using this model. The meropenem administration time of patients with CCr ≧ 85 mL/min should be extended as the standard dosing regimen cannot lead to the PTA of 50% T > MIC of 4 mcg/mL. Moreover, the administration time should be extended for patients with CCr ≧ 70 mL/min, and the dose should be increased to 2 g to achieve the PTA of 100% T > MIC of 4 mcg/mL. Therefore, the effectiveness of meropenem in patients with sepsis can be maximized by selecting the appropriate dosing regimen based on renal function and MIC.

Free Research Field

臨床薬学

Academic Significance and Societal Importance of the Research Achievements

本研究では実測CCrを用いた腎機能の正確な評価により、敗血症患者におけるMEPM血中濃度を正確に予測できるPPKモデルを構築した。また、本モデルを使用して、腎機能や原因菌のMIC別にPTA ≧ 90%を達成できる推奨投与レジメンを示すことができた。以上の結果から、敗血症患者にMEPMを投与する場合は、腎機能及び原因菌のMICに基づいた投与レジメンを選択することによりMEPMの効果を最大限に発揮できる可能性が示された。