Int. Journal of Clinical Pharmacology and Therapeutics, Volume 58 (2020) - January (50 - 56)

Pharmacokinetic/pharmacodynamic analysis of meropenem, by Monte Carlo simulation, in both plasma and cerebrospinal fluid in patients with cerebral hemorrhage after external ventricular drainage

Lingti Kong1, Hongzhou Xu2, Chenchen Wu3, Xiangxun Kong4, Meiling Yu1, Qingping Shi1, Xiaofei Wu2
1 Department of Pharmacy, 2 Department of Emergency Internal Medicine, 3 Department of Endocrinology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, and 4 Department of Oncology and Hematology, Heze Dingtao People’s Hospital, Heze, China

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DOI 10.5414/CP203606

Abstract

Objective: Patients with cerebral hemorrhage are often prone to intracranial infection, and meropenem is recommended for treatment. But whether the widely used dosing regimen (1 g, 2-hour infusion, every 12 hours) is suitable for antibiotic therapy is still unclear. The purpose of this study was to perform pharmacokinetic/pharmacodynamic (PK/PD) analyses of meropenem in both plasma and cerebrospinal fluid (CSF) in these patients.
Materials and methods: Ten patients were enrolled in the present study. The blood samples and CSF samples were taken at predetermined time points and determined by our previously developed HPLC method. Pharmacokinetic parameters were then calculated, and the probability of target attainment (PTA) was calculated by the time that drug concentrations were above the minimum inhibitory concentration (%T>MIC).
Results: The peak meropenem concentration (Cmax) of 17.79 ± 3.38 μg/mL in plasma was reached at 2 hours, and the area under the curve (AUC) was 46.95 ± 4.37 h×μg/mL. The Cmax of 6.51 ± 1.11 μg/mL in CSF was reached at 3.50 ± 0.53 hours, and the AUC was 24.53 ± 4.28 h×μg/mL. The average penetration rate of meropenem in these patients was 52.25%. In the case where the MIC value was ≤ 1 μg/mL and using 40%T>MIC as a PK/PD index, the PTA of meropenem in both plasma and CSF were able to provide good coverage with MIC ≤ 1 μg/mL.
Conclusion: In conclusion, this is the first study on the PK/PD analysis of meropenem in both plasma and CSF in patients with cerebral hemorrhage. The results will assist in selecting appropriate dosing regimens of meropenem in these patients.

Author Details

Authors

Departments

  • 1 Department of Pharmacy,
  • 2 Department of Emergency Internal Medicine,
  • 3 Department of Endocrinology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, and
  • 4 Department of Oncology and Hematology, Heze Dingtao People’s Hospital, Heze, China

Address

Xiaofei Wu, MD
Department of ­Emergency Internal Medicine
The First Affiliated Hospital of Bengbu Medical College
Bengbu, China
Email: [email protected]

Citation

Kong L, Xu H, Wu C, Kong X, Yu M, Shi Q, Wu X.Pharmacokinetic/pharmacodynamic analysis of meropenem, by Monte Carlo simulation, in both plasma and cerebrospinal fluid in patients with cerebral hemorrhage after external ventricular drainage
. Int J Clin Pharmacol Ther. 2020; 58: 50-56. doi: 10.5414/CP203606. Pubmed: https://www.ncbi.nlm.nih.gov/pubmed/31670654; PMID: 31670654.

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