Characterization of Histamine Release Induced by Fluoroquinolone Antibacterial Agents In-vivo and In-vitro


Drug Safety Research Laboratory, Daiichi Pharmaceutical Co. Ltd, 16-13 Kitakasai 1-chome, Edogawa-ku, Tokyo 134-8630, Japan., Accepted November 1, 1999, Accepted December 21, 1999


Characterization of histamine release induced by fluoroquinolone antibacterial agents, levofloxacin and ciprofloxacin, was investigated in-vivo and in-vitro.

Intravenous injection of levofloxacin and ciprofloxacin at 1–10 mg kg−1 produced dose-related elevations in plasma histamine level in anaesthetized dogs. In contrast, levofloxacin was devoid of plasma histamine increment in anaesthetized rats at 100 mg kg−1, whereas ciprofloxacin at the same dose caused endogenous histamine release. Levofloxacin and ciprofloxacin induced non-cytotoxic secretion of histamine from all mast cells tested in a concentration-dependent manner, whereas rat skin and peritoneal mast cells were thirty- to one-hundred-times less sensitive to the effect of fluoroquinolones as compared with the canine skin mast cells.

These results suggest that the functional heterogeneity of mast cells from different species in histamine releasing activity of fluoroquinolones may exist, and that mast cells from the dog appear to be particularly sensitive to the effect of the fluoroquinolones.