Effects of imipenem and meropenem on purine content of endothelial cells

Intravenous compatibility of antibacterial agents has been tested in animal models. Use of human umbilical venous endothelial cells (HUVEC) to test an tibiotic solutions for intravenous tolerance provides a valuable alternate model. Objective: Evaluation of the effect of imipenem and meropenem on int racellular purines reflecting viability, energy production, signal transduc tion, and DNA/RNA synthesis of these cells. Materials and methods: Levels o f intracellular adenosine 5' triphosphate (ATP), adenosine 5' diphosphate ( ADP), guanosine 5' triphosphate (GTP) and guanosine 5' diphosphate (GDP) we re measured by means of high performance liquid chromatography (HPLC). Resu lts: The total amount of ATP after incubation of cells with 10.0 mg/ml imip enem 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 6 0 minutes showed similar results. Purine nucleotide profiles of ADP, GTP, G DP following exposure of 10.0 mg/ml, 5.0 mg/ml and 2.5 mg/ml of imipenem an d meropenem did not differ markedly. Conclusions: These in vitro data show an excellent endothelial compatibility of imipenem and meropenem even in hi gh concentrations.