guanosine-diphosphate and trovafloxacin

Levofloxacin and trovafloxacin have excellent activity against a variety of Gram-positive and Gram-negative organisms resistant to the established agents. One local side-effect closely related to the use of parenteral fluoroquinolones is phlebitis. To evaluate the effect of trovafloxacin and levofloxacin on endothelial cell viability, intracellular levels of adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP), guanosine 5'-triphosphate (GTP) and guanosine 5'-diphosphate (GDP) levels were measured using high-performance liquid chromatography. Trovafloxacin at concentrations of 2 and 1 mg/mL reduced the intracellular ATP content from 12.5 +/- 1.7 to 1.9 +/- 0.3 nmol/10(6) cells and 9.3 +/- 0.8 nmol/10(6) cells, respectively, within 60 min. In addition, ADP, GTP and GDP levels were extensively depleted. Levofloxacin at concentrations of 5 and 2.5 mg/mL led to a significant ATP decline from 12.5 +/- 1.7 to 2.3 +/- 0.2 nmol/10(6) cells and 10.3 +/- 0.9 nmol/10(6) cells, respectively, within 60 min. These data indicate that infusions of high doses of trovafloxacin or levofloxacin are not compatible with maintenance of endothelial cell function. Commercial preparations have to be diluted and should be administered into large veins.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Anti-Infective Agents; Cell Survival; Chromatography, High Pressure Liquid; Culture Media; Endothelium, Vascular; Female; Fluoroquinolones; Guanosine Diphosphate; Guanosine Triphosphate; Humans; In Vitro Techniques; Levofloxacin; Naphthyridines; Ofloxacin; Pregnancy; Umbilical Veins