Abstract
The flush induced by two fluoroquinolone antibacterial agents, balofloxacin and ofloxacin, was studied in beagle dogs. Intradermal injection of the fluoroquinolones at concentrations above 10−5M produced a localized flushed area. The flush responses to fluoroquinolones were inhibited by co-administration with H2-antagonist(s) (ranitidine or cimetidine), but not with H1-antagonist(s) (mepyramine or chlorpheniramine). Similar inhibitory effects of these H2-antagonists were observed for the response to histamine. The flush responses to fluoroquinolones were inhibited by a local pretreatment with compound 48/80 administered to deplete the local stores of mast cell-bound histamine. When the fluoroquinolones were orally administered at a dose of 400 mg/kg, the concentration of histamine in plasma was increased, being accompanied by systemic erythema. These results indicate that the flush induced by fluoroquinolones is mediated by histamine release from canine cutaneous mast cells and H2-receptor stimulation.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Janknegt R. Fluoroquinolones. Adverse reactions during clinical trials and postmarketing surveillance. Pharm Weekbl 1989;11:124–7.
Feist H. Sequential therapy with i.v. and oral ofloxacin in lower respiratory tract infection: A comparative study. Infection 1991;19:S380–3.
Dávila I, Diez ML, Quirce S, Fraj J, De La Hoz B, Lazaro M. Cross-reactivity between quinolones. Report of three cases. Allergy 1993;48:388–90.
Takasuna K, Kasai Y, Usui C, Takahashi M, Hirohashi M, Tamura K, et al. General pharmacology of the new quinolone antibacterial agent levofloxacin. Arzneim Forsch Drug Res 1992;42:408–18.
Ito K, Murakami K, Tamura K.α1-Adrenoceptor-blocking activity of ofloxacin and ciprofloxacin in isolated vascular smooth muscles. Arch Int Pharmacodyn 1993;325:86–95.
Wagai N, Yamaguchi F, Sekiguchi M, Tawara K. Phototoxic potential of quinolone antibacterial agents in Balb/c mice. Toxicol Lett 1990;54:299–308.
Wagai N, Tawara K. Quinolone antibacterial-agent-induced cutaneous phototoxicity; ear swelling reactions in Balb/c mice. Toxicol Lett 1991;58:215–33.
Matsumoto M, Kojima K, Nagano H, Matsubara S, Yokota T. Photostability and biological activity of fluoroquinolones substituted at the 8 position after UV irradiation. Antimicrob Agents Chemother 1992;36:1715–9.
Marutani K, Matsumoto M, Otabe Y, Nagamuta M, Tanaka K, Miyoshi A, et al. Reduced phototoxicity of a fluoroquinolone antibacterial agent with a methoxy group at the 8 position in mice irradiated with long-wavelengh UV light. Antimicrob Agents Chemother 1993;37:2217–23.
Foreman JC, Jordan CC, Oehme P, Renner H. Structure-activity relationships for some substance P-related peptides that cause wheal and flare reactions in human skin. J Physiol 1983;335:449–65.
Hägermark Ö, Hökfelh T, Pernow B. Flare and itch induced by substance P in human skin. J Invest Dermatol 1978;71:233–5.
Owen DAA. Histamine receptors in the cardiovascular system. Gen Pharmacol 1977;8:141–56.
Black JW, Owen DAA, Parsons ME. An analysis of the depressor responses to histamine in the cat and dog: Involvement of both H1- and H2-receptors. Br J Pharmacol 1975;54:319–24.
Powell JR, Brody MJ. Identification and specific blockade of two receptors for histamine in the cardiovascular system. J Pharmacol Exp Ther 1976; 196:1–14.
Pawlik W, Tague LL, Tepperman BL, Miller TA, Jacobson ED. Histamine H1- and H2-receptor vasodilation of canine intestinal circulation. Am J Physiol 1977;233:E219–24.
Dobbins DE, Swindall BT, Haddy FJ, Dabney JM. Blockade of histamine-mediated increases in microvascular permeability by H1- and H2-receptor antagonists. Microvasc Res 1981;21:343–50.
Ennis M, Amon EU and Lorenz W. Histamine release from canine lung and liver mast cells induced by radiographic contrast media. Agents Actions 1989;27:101–3.
DeMora F, García G, Ferrer L and Arboix M. Canine cutaneous mast cells dispersion and histamine secretory characterization. Vet Immunol Immunopathol 1993;39:421–9.