Yet Another Doctor Blog On The Internet

The value of irbesartan in the management of hypertension.


Although many antihistamines are now in clinical use, few studies directly compare their pharmacodynamic and sedative activities in humans in vivo. We designed a double-blind, placebo-controlled, crossover study to compare the inhibitory effects of bepotastine, cetirizine, fexofenadine, and olopatadine on histamine-induced flare-and-wheal response. Systemic sedative effects and impaired psychomotor activities by these drugs were also evaluated. Bepotastine (10 mg twice a day), cetirizine (10 mg once a day), fexofenadine (60 mg twice a day), and olopatadine (5 mg twice a day) or placebo was given in a double-blind manner to seven healthy volunteers before histamine challenge by iontophoresis. At 0, 1, 2, 4, 8, 12, and 24 h following the oral administration of these drugs, histamine iontophoresis-induced wheal-and-flare response was measured. Sedative effects by the drugs were also evaluated by a visual analogue scale for subjective sedation, and by word processor test for psychomotor activity. Each volunteer was tested with all of the drugs (including placebo), administered in a random order with a washout period of at least 1 week. Histamine iontophoresis induced marked wheal-and-flare response in all participants. Bepotastine, cetirizine, fexofenadine, and olopatadine yielded significant reduction of histamine-induced wheal-and-flare response compared to placebo (P < 0.01). Among the drugs, olopatadine and cetirizine suppressed most markedly and persistently histamine-induced wheal-and-flare response, while bepotastine and fexofenadine produced a significant, but less persistent suppression. Olopatadine, fexofenadine, and cetirizine showed a significant systemic sedative effect in this order with bepotastine showing the least sedative effect. Moreover, olopatadine affected psychomotor performance most markedly, which was followed by fexofenadine and cetirizine. These results indicate that bepotastine, cetirizine, fexofenadine, and olopatadine inhibit histamine-induced wheal-and-flare response of humans in vivo and induce a variable systemic sedative effect and impaired psychomotor activity. Although olopatadine and cetirizine showed the strongest and most persistent suppression of histamine-induced wheal-and-flare response, olopatadine showed a considerable sedative effect with impaired psychomotor performance.

Keratinocytes participate in initiation and amplification of T-cell-mediated skin diseases. During these disorders, histamine can be released from both residents skin cells and immigrating leukocytes, and can affect the functions of dendritic cells, monocytes, and lymphocytes. Little information is available on the effects of histamine on keratinocytes.

Compared with the control group of dermal fibroblast (DF) cells and HaCaT cells, MCP-1 mRNA was significantly upregulated by histamine (10 micromol x L(-1)) and IFN-gamma (20 ng x mL(-1)). The protein secretions of MCP-1 were increased 3.5 fold and 8.4 fold in DF cells, respectively. The similar tendency was observed in HaCaT cells. The enhancing effects of histamine and IFN-gamma on MCP-1 protein production were significantly inhibited by cetirizine (1 and 10 micromol x L(-1)) in DF and HaCaT cells.

The new H1-receptor antagonist, cetirizine, is eliminated primarily unchanged by renal excretion and is thus potentially useful for relief of pruritus in patients with hepatic dysfunction, in whom many H1-receptor antagonists are contraindicated. The authors studied the elimination of cetirizine in six patients with primary biliary cirrhosis. In contrast to data obtained in healthy adults with normal hepatic function reported in the medical literature, they found that the mean serum elimination half-life value of cetirizine, 13.8 +/- 1.8 hours, was longer, and the mean clearance rate, 0.44 +/- 0.10 mL/min/kg, was lower (P < .05). The mean peak serum cetirizine concentration, 498 +/- 118 ng/mL, was higher, the mean area under the curve, 6438 +/- 1621 ng/mL/hr, was larger, and the mean fraction of the dose excreted as unchanged cetirizine in the urine, .32 +/- .14, was lower (P < .05). The duration of action of cetirizine was prolonged, as evidenced by significant suppression of the histamine-induced wheal and flare for 48 and 72 hours, respectively, after a single dose. Cetirizine elimination was impaired in patients with hepatic dysfunction.

The small sample size and single dose design of this study prevent definitive conclusions regarding the pharmacokinetics and safety of levocetirizine OS in a Japanese patient population being made. Study limitations include conducting the study in adult males, not in children.

All patients were sensitive to visible light (median MUD 50 J/cm(2)). Three patients were sensitive to UVA (median MUD 3.75 J/cm(2)), and one patient was sensitive to UVB (MUD of 0.03 J/cm(2)). Two patients experienced a spontaneous remission without treatment. One patient declined treatment. The remaining eight patients were managed by a combination of antihistamines (desloratidine, fexofenadine, cetirizine HCl) and a leukotriene receptor antagonist (montelukast). Seven of the 8 patients experienced a sustained remission of symptoms and signs following treatment.