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.