Author(s)

Min Luo^1,4,5#, Wei Bu^1,4#, Lu Yao^1,4, Liu Shi^1,4, HongBo Xu³, WenMei Liang¹, Yan Chen³, Tao Chen¹, Bao Fu^1*, Lei Gong^1,2*

Affiliation(s)

¹Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou, China.

²Department of Pharmaceutics, Kweichow Moutai Hospital, Zunyi 563000, Guizhou, China.

³Guizhou Children's Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou, China.

⁴School of Pharmacy, Zunyi Medical University, Zunyi 563000, Guizhou, China.

⁵Zhijin County People's Hospital, Bijie 552102, Guizhou, China.

Corresponding Author

Bao Fu, Lei Gong

ABSTRACT

Objective: To establish a population pharmacokinetic (PPK) model for meropenem in patients with severe acute pancreatitis (SAP), providing a valuable basis and method for developing individualized meropenem dosing regimens tailored to the pathophysiological state of SAP patients; Methods: Meropenem concentrations in plasma and abdominal drainage fluid were monitored using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and homogeneous enzyme immunoassay. Nonlinear mixed-effects modeling was performed using Phoenix software; Results: (1) Meropenem concentration determination: A total of 20 SAP patients were enrolled, providing 99 qualified plasma samples and 42 qualified abdominal drainage fluid samples. Meropenem and the internal standard (metformin) were well separated in both plasma and drainage fluid samples, demonstrating good specificity. Meropenem showed excellent linearity within the ranges of 0.5 - 200 μg/mL in plasma and 0.1 - 10 μg/mL in drainage fluid. All methodological validation results fell within acceptable limits, with RSD ≤ 15%; Conclusion: This study established an LC-MS/MS method (referenced and quality-controlled by homogeneous enzyme immunoassay) for determining meropenem concentrations. The validated method is suitable for clinical therapeutic drug monitoring (TDM) of meropenem, particularly in critically ill ICU patients.

KEYWORDS

Meropenem; Severe acute pancreatitis; Therapeutic drug monitoring; Monte Carlo simulation; Pharmacokinetics/Pharmacodynamics; Individualized therapy

CITE THIS PAPER

Min Luo, Wei Bu, Lu Yao, Liu Shi, HongBo Xu, WenMei Liang, Yan Chen, Tao Chen, Bao Fu, Lei Gong. Establishment of a method for monitoring meropenem concentrations in patients with severe acute pancreatitis. Journal of Pharmaceutical and Medical Research. 2025, 7(2): 31-36. DOI: https://doi.org/10.61784/jpmr3042.

REFERENCES

[1] Zylbersztajn B, Parker S, Navea D, et al. Population Pharmacokinetics of Vancomycin and Meropenem in Pediatric Extracorporeal Membrane Oxygenation Support. Frontiers in Pharmacology, 2021, 12: 709332.

[2] Tan WW, Watt KM, Boakye-Agyeman F, et al. Optimal dosing of meropenem in a small cohort of critically ill children receiving continuous renal replacement therapy. Journal of Clinical Pharmacology, 2021, 61(6): 744-754.

[3] He J, Xu SL, Shao H, et al. Optimization of blood concentration monitoring method for meropenem application in critically ill patients and clinical application examples. Chinese Journal of Hospital Pharmacy (Zhongguo Yiyuan Yaoxue Zazhi), 2018, 38(04): 416-419.

[4] Zhang WD, Zhang WW, Yan Y, et al. Determination of meropenem concentration in human plasma by liquid chromatography-tandem mass spectrometry and its application in therapeutic drug monitoring of ICU sepsis patients. Journal of Hebei Medical University (Hebei Yike Daxue Xuebao), 2022, 43(11): 1286-1290.

[5] Lyu JX, Xu WJ, Zhao J, et al. Simultaneous determination of 5 antibacterial drugs in human plasma by LC-MS and its application in critically ill patients. Chinese Journal of Hospital Pharmacy (Zhongguo Yiyuan Yaoxue Zazhi), 2023: 1-9.

[6] Zhu DP, Luo JM, Cai XJ. Study on the determination of meropenem concentration in human serum by ultra performance liquid chromatography-tandem mass spectrometry. Zhejiang Journal of Integrative Traditional Chinese and Western Medicine (Zhejiang Zhongxiyi Jiehe Zazhi), 2023, 33(11): 1052-1055.

[7] Ferrone V, Cotellese R, Cichella A, et al. Meropenem and ciprofloxacin in complicated gastric surgery for cancer patients: A simple SPE-UHPLC-PDA method for their determination in human plasma. Biomedical Chromatography, 2019, 33(3): e4450.

[8] D'Cunha R, Bach T, Young BA, et al. Quantification of cefepime, meropenem, piperacillin, and tazobactam in human plasma using a sensitive and robust liquid chromatography-tandem mass spectrometry method, part 2: stability evaluation. Antimicrob Agents Chemother, 2018, 62(9): e00859-18.

[9] Rao Z, Dang ZL, Bin L, et al. Determination of total and unbound meropenem, imipenem/cilastatin, and cefoperazone/sulbactam in human plasma: application for therapeutic drug monitoring in critically ill patients. Therapeutic Drug Monitoring, 2020, 42(4): 578-587.

[10] Dincel D, Sagirli O, Topcu G. A high-performance liquid chromatographic method for the determination of meropenem in serum. Journal of Chromatographic Science, 2020, 58(2): 144-150.

[11] Zou L, Meng F, Hu L, et al. A novel reversed-phase high-performance liquid chromatographic assay for the simultaneous determination of imipenem and meropenem in human plasma and its application in TDM. Journal of Pharmaceutical and Biomedical Analysis, 2019, 169: 142-150.