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Effects of imipenem and meropenem on purine content of endothelial cells
C Armbruster1, H Vorbach, B Robibaro
12nd Medical Department/Pulmologisches Zentrum, Vienna, Austria.
Unlabelled:
Intravenous compatibility of antibacterial agents has been tested in animal models. Use of human umbilical venous endothelial cells (HUVEC) to test antibiotic solutions for intravenous tolerance provides a valuable alternate model.
Objective:
Evaluation of the effect of imipenem and meropenem on intracellular purines reflecting viability, energy production, signal transduction, and DNA/RNA synthesis of these cells.
Materials And Methods:
Levels of intracellular adenosine 5' triphosphate (ATP), adenosine 5' diphosphate (ADP), guanosine 5' triphosphate (GTP) and guanosine 5' diphosphate (GDP) were measured by means of high performance liquid chromatography (HPLC).
Results:
The total amount of ATP after incubation of cells with 10.0 mg/ml imipenem and meropenem for 20 minutes (12.93 +/- 0.93 nmol/million cells and 13.27 +/- 0.89 nmol/million cells, respectively) did not result in a decrease compared to controls (12.34 +/- 0.87 nmol/million cells). In addition, ATP levels were maintained or actually increased after 60 minutes. Incubation of cells with 5.0 mg/ml and 2.5 mg/ml of imipenem or meropenem for 20 and 60 minutes showed similar results. Purine nucleotide profiles of ADP, GTP, GDP following exposure of 10.0 mg/ml, 5.0 mg/ml and 2.5 mg/ml of imipenem and meropenem did not differ markedly.
Conclusions:
These in vitro data show an excellent endothelial compatibility of imipenem and meropenem even in high concentrations.
Insights
Imipenem and meropenem show excellent intravenous compatibility in human umbilical venous endothelial cells (HUVEC). These antibiotics maintained or increased intracellular purine levels, indicating good endothelial cell viability and function.
Area of Science:
- Endothelial cell biology
- Pharmacology
- Biochemistry
Background:
- Intravenous compatibility of antibacterial agents is crucial for patient safety.
- Traditional animal models for testing intravenous tolerance have limitations.
- Human umbilical venous endothelial cells (HUVEC) offer a valuable in vitro model for assessing drug compatibility.
Purpose of the Study:
- To evaluate the effect of imipenem and meropenem on intracellular purine levels in HUVEC.
- To assess the impact of these antibiotics on cell viability, energy production, signal transduction, and nucleic acid synthesis.
- To determine the endothelial compatibility of imipenem and meropenem in vitro.
Main Methods:
- Intracellular adenosine 5' triphosphate (ATP), ADP, guanosine 5' triphosphate (GTP), and GDP levels were quantified.
- High-performance liquid chromatography (HPLC) was employed for precise measurement of purine nucleotides.
- HUVEC were exposed to varying concentrations of imipenem and meropenem (10.0, 5.0, and 2.5 mg/ml) for 20 and 60 minutes.
Main Results:
- Incubation with 10.0 mg/ml imipenem and meropenem did not decrease ATP levels compared to controls after 20 minutes.
- ATP levels were maintained or increased after 60 minutes of exposure to these antibiotics.
- No significant differences in ADP, GTP, and GDP levels were observed across various concentrations and incubation times.
Conclusions:
- Imipenem and meropenem demonstrate excellent endothelial compatibility in vitro.
- High concentrations of these antibiotics do not adversely affect intracellular purine metabolism in HUVEC.
- These findings support the safe intravenous administration of imipenem and meropenem.