A Comparison of Cetirizine, Ebastine,  Epinastine, Fexofenadine, Terfenadine, and  Loratadine versus Placebo in Suppressing  the Cutaneous Response to Histamine

Danielson, Linda; Rihoux, J P; Devos, C

doi:10.1159/000024126

Cited by 11 publications

(6 citation statements)

References 4 publications

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“…4). Previous reports showed that cetirizine has a maximal effect on histamine-induced dermal reactions at jpet.aspetjournals.org 4-8 hours, which is consistent with that seen here (Coulie et al, 1989(Coulie et al, , 1991bSimons et al, 1990;Lahti and Haapaniemi, 1993;Grant et al, 1999;Furue et al, 2001;Morita et al, 2005).…”

Section: Resultssupporting

confidence: 90%

“…Both of these effects were almost completely eliminated by the H 1 R antagonist, cetirizine, which is consistent with previous reports (Juhlin et al, 1987;Coulie et al, 1989Coulie et al, , 1991aSimons et al, 1990;Levander et al, 1991;Lahti and Haapaniemi, 1993;Grant , 1999;Furue et al, 2001;Morita et al, 2005). The ability of histamine to induce a wheal response is due to the expression of H 1 R on endothelial cells that control vascular permeability; thus, all compounds that inhibit the H 1 R will inhibit wheal responses.…”

Section: Discussionsupporting

confidence: 90%

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The Histamine H₄Receptor Antagonist, JNJ 39758979, Is Effective in Reducing Histamine-Induced Pruritus in a Randomized Clinical Study in Healthy Subjects

Kollmeier

Francke

Chen

et al. 2014

J Pharmacol Exp Ther

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The histamine H 4 receptor (H 4 R) is a promising target for the treatment of pruritus. A clinical study was conducted to evaluate the safety and efficacy of the H 4 R antagonist, JNJ 39758979 [(R)-4-(3-amino-pyrrolidin-1-yl)-6-isopropyl-pyrimidin-2-ylamine], on histamine-induced pruritus in healthy subjects. A single oral dose of 600 mg JNJ 39758979, 10 mg cetirizine, or placebo was administered in a randomized, three-period, double-blind, crossover study. Treatment periods were separated by 22-day washout periods. A histamine challenge was administered on day 21 and at 2 and 6 hours postdose on day 1 of each treatment period. The primary efficacy endpoint was the area under the curve (AUC) of pruritus score 0-10 minutes after the histamine challenge. Secondary efficacy endpoints included wheal and flare areas assessed 10 minutes after the histamine challenge. Safety was assessed for all subjects. Of the 24 enrolled subjects, 23 individuals completed the study. One subject withdrew after completing two treatment periods. Due to a carryover effect of JNJ 39758979, only treatment period 1 was used for pruritus-related evaluations. Compared with placebo, the reduction of the AUC of pruritus score was significant for JNJ 39758979 at 2 hours (P 5 0.0248) and 6 hours (P 5 0.0060), and for cetirizine at 6 hours (P 5 0.0417). In all treatment periods, JNJ 39758979 did not demonstrate a significant decrease in wheal or flare at either time point, although a significant reduction was achieved with cetirizine at 2 and 6 hours (P , 0.0001). Adverse eventss reported in .1 patient with JNJ 39758979 were headache (9%) and nausea (13%). In conclusion, JNJ 39758979 was effective in inhibiting histamine-induced pruritus in healthy subjects.

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Section: Resultssupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

The Histamine H₄Receptor Antagonist, JNJ 39758979, Is Effective in Reducing Histamine-Induced Pruritus in a Randomized Clinical Study in Healthy Subjects

Kollmeier

Francke

Chen

et al. 2014

J Pharmacol Exp Ther

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“…To determine whether the effects of an oral dose of an H1 histamine receptor antagonist could attenuate the vasodilatation to exogenous histamine in a fashion similar to studies in which we delivered an H1 antagonist via microdialysis, we performed studies on four subjects who were administered 360 mg orally of the second‐generation H1 antagonist fexofenadine. Based on previous data, we infused histamine via microdialysis and observed the skin blood flow response 1 h after fexofenadine ingestion, which corresponds to peak plasma concentrations of fexofenadine, as well as at time points corresponding to peak concentrations in human skin (4 and 6 h post‐ingestion) (Russel et al 1998; Grant et al 1999 a , b ). In no case did we observe an attenuation of the cutaneous vasodilatation due to exogenous histamine infusion with oral fexofenadine.…”

Section: Discussionmentioning

confidence: 99%

“…Two subjects ingested fexofenadine 1 h prior to histamine infusion and two subjects ingested fexofenadine 4 h prior to arrival at the laboratory. Ingestion of fexofenadine at these two time periods corresponded to peak plasma and skin concentrations of fexofenadine (Russel et al 1998; Grant et al 1999 a , b ), respectively, prior to infusion of exogenous histamine. The first microdialysis site was continuously perfused with sterile Ringer solution and served as a control to examine the efficacy of oral fexofenadine to exogenous histamine.…”

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confidence: 99%

H1 but not H2 histamine receptor activation contributes to the rise in skin blood flow during whole body heating in humans

Wong

Wilkins

Minson

2004

The Journal of Physiology

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Recent evidence suggests a role for vasoactive intestinal polypeptide (VIP) in active vasodilatation and it has been shown that VIP-mediated vasodilatation includes a nitric oxide (NO) and histamine component. Thus, the purpose of this study was to determine the role of H1 and H2 histamine receptors and to examine a potential interaction between NO and histamine receptors in cutaneous active vasodilatation. Eleven subjects were instrumented with four microdialysis fibres. Site 1 served as a control and site 2 was perfused with L-NAME to inhibit nitric oxide synthase. Site 3 was perfused with either the H1 antagonist pyrilamine maleate or the H2 antagonist cimetidine. Site 4 was perfused with L-NAME plus pyrilamine maleate or L-NAME plus cimetidine. Laser-Doppler flowmetry (LDF) was used as an index of skin blood flow and cutaneous vascular conductance (CVC) was calculated as LDF/mean arterial pressure and normalized to maximal vasodilatation achieved via 28 mM sodium nitroprusside infusion. During whole body heating, subjects' sublingual temperature increased a minimum of 0.8• C. In the H1 antagonist studies, CVC in L-NAME, pyrilamine, and combined L-NAME plus pyrilamine sites was significantly reduced compared with control (P < 0.001). The L-NAME and combined L-NAME plus pyrilamine sites were significantly reduced compared with pyrilamine only sites (P < 0.05) but no significant differences were observed between sites. In the H2 receptor antagonist studies, CVC in control sites was not significantly different from cimetidine sites. There was no difference between the L-NAME and combined L-NAME plus cimetidine sites but these sites were significantly attenuated compared with control and cimetidine only sites (P < 0.05). These data suggest the rise in skin blood flow during whole body heating contains an H1 histamine receptor component but do not support an H2 histamine receptor component. Furthermore, part of the NO-dependent component of active vasodilatation can be explained by H1 receptor activation.

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“…First, is an antihistamine effect compatible with so small a V D ? The answer is obviously yes, since this drug was shown to be the most potent H 1 antagonist in humans at skin and bronchial levels (8,9) and its clinical efficacy has been clearly demonstrated (10). Second, is such a V D an advantage, a disadvantage, or a curiosity devoid of any clinical significance?…”

Section: Apparent Vd Of H1 Receptor Antagonistsmentioning

confidence: 99%

The apparent volumes of distribution of H ₁ receptor antagonists

Tillement

Albengres

Barré

et al. 2000

Dermatologic Therapy

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The apparent volume of distribution (VD) of a drug estimates its distribution into the body. Referring to the volume of exchangeable water (0.6 L/kg body weight), it indicates if tissue distribution is extensive when VD is greater than 0.6 L/kg or poor if VD is less than 0.6 L/kg. Its interest in the selection of an appropriate drug is found after comparing the map of selected targets (mainly receptors) to be reached by the drug, the accessibility of these targets by the drug, and the VD necessary and sufficient to reach them. This analysis is here applied to H1 receptor antagonists, a pharmacologic class, where target cells, endothelial cells such as eosinophils, mastocytes, basophils, and smooth fibers have receptors on the external side of cell membranes and thus are more readily accessible from blood than toxic sites located inside cells (heart, brain, liver). Of the H1 receptor antagonists marketed today, cetirizine has the lowest VD, 0.4 L/kg, enough to reach selected targets without extensive distribution in organs where it would be useless. These characteristics are related to its chemical amphoteric structure.

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A Comparison of Cetirizine, Ebastine, Epinastine, Fexofenadine, Terfenadine, and Loratadine versus Placebo in Suppressing the Cutaneous Response to Histamine

Cited by 11 publications

References 4 publications

The Histamine H₄Receptor Antagonist, JNJ 39758979, Is Effective in Reducing Histamine-Induced Pruritus in a Randomized Clinical Study in Healthy Subjects

The Histamine H₄Receptor Antagonist, JNJ 39758979, Is Effective in Reducing Histamine-Induced Pruritus in a Randomized Clinical Study in Healthy Subjects

H1 but not H2 histamine receptor activation contributes to the rise in skin blood flow during whole body heating in humans

The apparent volumes of distribution of H ₁ receptor antagonists

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A Comparison of Cetirizine, Ebastine, Epinastine, Fexofenadine, Terfenadine, and Loratadine versus Placebo in Suppressing the Cutaneous Response to Histamine

Cited by 11 publications

References 4 publications

The Histamine H4Receptor Antagonist, JNJ 39758979, Is Effective in Reducing Histamine-Induced Pruritus in a Randomized Clinical Study in Healthy Subjects

The Histamine H4Receptor Antagonist, JNJ 39758979, Is Effective in Reducing Histamine-Induced Pruritus in a Randomized Clinical Study in Healthy Subjects

H1 but not H2 histamine receptor activation contributes to the rise in skin blood flow during whole body heating in humans

The apparent volumes of distribution of H 1 receptor antagonists

Contact Info

Product

Resources

About

The Histamine H₄Receptor Antagonist, JNJ 39758979, Is Effective in Reducing Histamine-Induced Pruritus in a Randomized Clinical Study in Healthy Subjects

The Histamine H₄Receptor Antagonist, JNJ 39758979, Is Effective in Reducing Histamine-Induced Pruritus in a Randomized Clinical Study in Healthy Subjects

The apparent volumes of distribution of H ₁ receptor antagonists