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Endothelial cell compatibility of azithromycin and erythromycin
H Vorbach1, C Armbruster, B Robibaro
1Department of Internal Medicine II, Pulmonary Centre, Vienna, Austria.
Abstract:
Phlebitis is a severe local adverse event related to the use of parenteral macrolides. In order to evaluate the effect of azithromycin and erythromycin on human venous endothelial cells, we set up an in vitro model. The intracellular levels of purine nucleotides, as adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP) and guanosine 5'-triphosphate (GTP), were measured by means of high-performance liquid chromatography. Incubation of cells with 2 mg/mL azithromycin and erythromycin resulted in a rapid decline of intracellular ATP from 12.5 +/- 0.9 nmol/million cells to 4.1 +/- 0.3 and 2.6 +/- 0.4 nmol/million cells, respectively, after 60 min. In addition, ADP was extensively depleted from 2.1 +/- 0.17 nmol/million cells to 0.8 +/- 0.09 and 0.8 +/- 0.13 nmol/million cells after 60 min. After exposure of 0.5 mg/mL azithromycin and erythromycin, no significant decline of intracellular high-energy phosphate levels occurred after 20 and 60 min. Based on these results, solutions of azithromycin and erythromycin may not be well tolerated and may cause local adverse reactions even if diluted according to the manufacturer's recommendation.
Insights
Parenteral macrolides like azithromycin and erythromycin can cause phlebitis. High concentrations significantly deplete cellular energy, suggesting potential for local adverse reactions even when diluted.
Area of Science:
- Pharmacology
- Cell Biology
- Biochemistry
Background:
- Phlebitis is a significant adverse event linked to parenteral macrolide antibiotic use.
- Understanding the cellular mechanisms behind macrolide-induced phlebitis is crucial for patient safety.
Purpose of the Study:
- To investigate the in vitro effects of azithromycin and erythromycin on human venous endothelial cells.
- To assess the impact of these macrolides on intracellular purine nucleotide levels.
Main Methods:
- An in vitro model using human venous endothelial cells was established.
- High-performance liquid chromatography (HPLC) was employed to measure intracellular adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP), and guanosine 5'-triphosphate (GTP) levels.
- Cells were incubated with varying concentrations of azithromycin and erythromycin.
Main Results:
- Incubation with 2 mg/mL azithromycin and erythromycin led to a rapid and substantial decrease in intracellular ATP and ADP levels within 60 minutes.
- Lower concentrations (0.5 mg/mL) of these macrolides did not cause significant depletion of high-energy phosphates after 20 or 60 minutes.
- The observed depletion of cellular energy stores suggests a direct cellular impact.
Conclusions:
- High concentrations of azithromycin and erythromycin significantly disrupt cellular energy metabolism in human venous endothelial cells.
- These findings suggest that azithromycin and erythromycin solutions may cause local adverse reactions, including phlebitis, due to their impact on venous tissue.
- Dilution according to manufacturer recommendations may not fully mitigate the risk of local intolerance.