Endothelial cell compatibility of clarithromycin for intravenous use

Objectives: Tolerance of intravenously applied clarithromycin has been test ed on marginal ear veins of rabbits. Use of human umbilical Venous endothel ial cells (HUVEC) for testing antibiotic solutions for intravenous compatib ility provides a Valuable alternate model. Design and methods: In order to evaluate the effect of clarithromycin on in tracellular purines, reflecting cell viability, energy production, signal t ransduction and DNA/RNA synthesis, intracellular adenosine 5' triphosphate (ATP), adenosine 5' diphosphate (ADP), guanosine 5' triphosphate (GTP), and guanosine 5' diphosphate (GDP) levels were measured by means of high perfo rmance liquid chromatography (HPLC). Results: Incubation of cells with 2 mg/mL clarithromycin resulted in a rapi d decrease of the intracellular ATP from 12.6 +/- 1.1 to 8.87 +/- 0.82 nmol /million cells or 1.5 +/- 0.6 nmol/million cells, after 20 or 60 min, respe ctively. In addition, ADP was extensively depleted. Purine nucleotide profi les were markedly different following exposure to 1 mg/mL clarithromycin. T here was no significant decline of intracellular high energy phosphate leve ls after 20 min. Conclusion: These results show that clarithromycin has a better endothelial compatibility if diluted to a final concentration of 1 mg/mL. These data a re in line with our clinical observations that the occurrence of phlebitis could be minimized by diluting the manufacturers' preparation of clarithrom ycin to 1 mg/mL. (C) 1998 The Canadian Society of Clinical Chemists.