Endothelial cell compatibility of clarithromycin for intravenous use.
OBJECTIVE
Tolerance of intravenously applied clarithromycin has been tested on marginal ear veins of rabbits. Use of human umbilical venous endothelial cells (HUVEC) for testing antibiotic solutions for intravenous compatibility provides a valuable alternate model.


METHODS
In order to evaluate the effect of clarithromycin on intracellular purines, reflecting cell viability, energy production, signal transduction 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 performance liquid chromatography (HPLC).


RESULTS
Incubation of cells with 2 mg/mL clarithromycin resulted in a rapid 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, respectively. In addition, ADP was extensively depleted. Purine nucleotide profiles were markedly different following exposure to 1 mg/mL clarithromycin. There was no significant decline of intracellular high energy phosphate levels after 20 min.


CONCLUSIONS
These results show that clarithromycin has a better endothelial compatibility if diluted to a final concentration of 1 mg/mL. These data are in line with our clinical observations that the occurrence of phlebitis could be minimized by diluting the manufacturers' preparation of clarithromycin to 1 mg/mL.
Vorbach
H
H
Department of Internal Medicine II, University Hospital of Vienna, Austria.
Weigel
G
G
Robibaro
B
B
Armbruster
C
C
Schaumann
R
R
Hlousek
M
M
Reiter
M
M
Griesmacher
A
A
Georgopoulos
A
A
D000225:Adenine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D017291:Clarithromycin / Q000008:administration & dosage* / Q000009:adverse effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D006147:Guanine / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D011817:Rabbits; D018709:Statistics, Nonparametric; D014471:Umbilical Veins
D006147:Guanine; D000255:Adenosine Triphosphate; D017291:Clarithromycin; D000225:Adenine