| Description |
Cetrizine is thought to block or reduce PGD2 which has been shown to supress hair growth.
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| Typical Results |
This seems to be a very new treatment(mid 2012) option but some users are reporting substantial regrowth in areas that were bald
of terminal hairs.
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| Typical Dosages |
Still being tested.
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| Significant Side Effects |
None reported
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| Pharmacology Pharmacodynamics |
Mechanism of Actions
Cetirizine, a human metabolite of hydroxyzine, is an antihistamine; its principal effects are mediated via selective inhibition of peripheral H1 receptors. The antihistaminic activity of Cetirizine has been clearly documented in a variety of animal and human models. In vivo and ex vivo animal models have shown negligible anticholinergic and antiserotonergic activity. In clinical studies, however, dry mouth was more common with Cetirizine than with placebo. In vitro receptor binding studies have shown no measurable affinity for other than H1 receptors. Autoradiographic studies with radiolabeled Cetirizine in the rat have shown negligible penetration into the brain. Ex vivo experiments in the mouse have shown that systemically administered Cetirizine does not significantly occupy cerebral H1 receptors.
Pharmacokinetics
Absorption
Cetirizine was rapidly absorbed with a time to maximum concentration (Tmax) of approximately 1 hour following oral administration of tablets or syrup in adults. Comparable bioavailability was found between the tablet and syrup dosage forms. When healthy volunteers were administered multiple doses of Cetirizine (10 mg tablets once daily for 10 days), a mean peak plasma concentration (Cmax) of 311 ng/mL was observed. No accumulation was observed. Cetirizine pharmacokinetics were linear for oral doses ranging from 5 to 60 mg. Food had no effect on the extent of Cetirizine exposure (AUC) but Tmax was delayed by 1.7 hours and Cmax was decreased by 23% in the presence of food.
Distribution
The mean plasma protein binding of Cetirizine is 93%, independent of concentration in the range of 25 to 1000 ng/mL, which includes the therapeutic plasma levels observed.
Metabolism
A mass balance study in 6 healthy male volunteers indicated that 70% of the administered radioactivity was recovered in the urine and 10% in the feces. Approximately 50% of the radioactivity was identified in the urine as unchanged drug. Most of the rapid increase in peak plasma radioactivity was associated with parent drug, suggesting a low degree of first-pass metabolism. Cetirizine is metabolized to a limited extent by oxidative O-dealkylation to a metabolite with negligible antihistaminic activity. The enzyme or enzymes responsible for this metabolism have not been identified.
Elimination
The mean elimination half-life in 146 healthy volunteers across multiple pharmacokinetic studies was 8.3 hours and the apparent total body clearance for Cetirizine was approximately 53 mL/min
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| Clinical Studies | Abstract |
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Therapeutic hotline. Effectiveness of the association of cetirizine and topical steroids in lichen planus pilaris--an open-label clinical trial..
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Lichen planus is considered a T cell-mediated immunological disease. Even mast cells may contribute to the pathogenesis of the disease. Keratinocytes of the basal layer of the skin and/or the hair follicle may represent the "target/victim" of an immune aggression, determining the destruction of the hair follicle and thus scarring alopecia. Therefore, there is a compelling urgency for effective treatment of this potentially disfiguring dermatosis. Our data provide a further therapeutic opportunity: the use of an antihistaminic drug--cetirizine (CTZ)--in an "anti-inflammatory" regimen. We propose the use of CTZ at the dosage of 30 mg/daily. Twenty-one patients affected by lichen planus pilaris (LPP) of the scalp have been treated. Topical application of steroids has been coadministered in all cases during the therapy. Clinical effects, in the sense of stabilization with cessation of the inflammation (erythema, follicular hyperkeratosis, loss of anagen hair), were achieved in all patients but three. One patient developed cardiac arrhythmia after 3 months of successful treatment and dropped out. Our cases indicate that a combined therapy of topical steroid with CTZ can be a safe and effective choice even in severe cases of lichen planus pilaris, so often refractory to the therapy.
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Effect of cetirizine on mast cell-mediator release and cellular traffic during the cutaneous late-phase reaction.
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A new H1 antihistamine, cetirizine, was studied to determine its effects on mediators and cellular infiltration during the cutaneous late-phase response (LPR). Ten ragweed-allergic subjects, who had previously demonstrated a cutaneous LPR, were examined in a double-blind, crossover study. Either cetirizine, 20 mg, or placebo was administered orally once daily for 2 days before and the morning of placement of a skin chamber overlying an unroofed heat/suction-induced blister to which was added antigen or buffer. Skin test erythema was significantly reduced by cetirizine at 15 minutes, 2 hours, and 4 hours by 56%, 40%, and 39%, respectively (all, p less than or equal to 0.01), but by 6 and at 8 hours, the cutaneous erythema was not significantly lessened. Histamine release was not altered by cetirizine treatment, but prostaglandin D2 (PGD2) production, which peaked at 3 to 5 hours, was clearly reduced by cetirizine treatment, being lower at all time points during the reaction; this was significant by analysis of variance (p less than or equal to 0.04). The inhibition was most marked during the fifth hour of the reaction when there was a 50% suppression of the PGD2 level by cetirizine (0.193 ng/ml to 0.075 ng/ml [p less than or equal to 0.03]). The most dramatic effect of cetirizine was attenuation of the inflammatory cell migration into the chamber. Eosinophil infiltration was decreased by about 75% during hours 6, 7, and 8 (p less than or equal to 0.04), whereas the number of neutrophils was reduced by the same magnitude at the same times (p less than or equal to 0.04).
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Inflammatory skin responses induced by icatibant injection are mast cell mediated and attenuated by H(1)-antihistamines..
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Icatibant, a bradykinin-2 receptor antagonist, is administered by subcutaneous injection for the treatment of attacks of type I and type II hereditary angioedema. Following injection, patients feel transient pain followed by a short-lived wheal and flare response at the injection site. We hypothesized that the icatibant-induced wheal and flare response follows histamine release from activated skin mast cells and would therefore be reduced by an H(1)-antihistamine. Intradermal injection of 100 μl of 100 μg/ml histamine and 10 mg/ml icatibant into the forearms of health volunteers caused wheal and flare responses of a similar magnitude which were reduced by cetirizine pretreatment by 49% and 41% (histamine) and 35% and 41% (icatibant). Studies in vitro showed that icatibant at 1 × 10(-4) and 1 × 10(-5) M caused significant (P < 0.05) histamine release from isolated human cutaneous mast cells. In conclusion, icatibant induces histamine-mediated wheal and flare responses that may be reduced in severity by prophylactic administration of an H(1)-antihistamine.
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Cetirizine inhibits skin reactions but not mediator release in immediate and developing late-phase allergic cutaneous reactions. A double-blind, placebo-controlled study..
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BACKGROUND:
Recent reports have indicated cetirizine, a potent H(1)-receptor antagonist, to possess a number of anti-inflammatory effects, e.g. inhibition of mast cell degranulation and inhibition of leucocyte migration and activation.
OBJECTIVE:
The aim of this study was to compare the effects of cetirizine on skin responses and mediator release in intact skin in immediate and developing late-phase allergic reactions by microdialysis technique.
METHODS:
Cetirizine 10 mg once daily or matching placebo were administered to 10 atopic subjects for 6 days followed by a 2-week washout in a randomized, double-blind, placebo-controlled, cross-over trial. Immediate skin test responses to allergen, codeine, and histamine and late-phase reactions to allergen were assessed. The time course of extracellular levels of inflammatory mediators in intact skin were monitored by microdialysis techniques using 2 kDa and 3 MDa cut-off fibers, respectively.
RESULTS:
Cetirizine significantly reduced immediate weal and flare reactions to allergen, codeine, and histamine. Injection of allergen, but not buffer controls, induced a significant release of histamine, tryptase, prostaglandin D(2), total protein, and eosinophilic cationic protein. No significant increase of leukotriene B(4) and myeloperoxidase was observed. Cetirizine inhibited early total protein extravasation by 40%, but this did not reach a significant level. None of the inflammatory mediators were significantly inhibited by cetirizine. Cetirizine significantly reduced the late-phase skin induration to allergen by approximately 30%.
CONCLUSION:
Cetirizine potently reduced skin responses in immediate allergic reactions without inhibition of early mediators. These data indicate cetirizine to be a potent H1-receptor antagonist with no effect on mast cell activation. It did not inhibit any of the late-phase mediators, but it reduced the late skin reaction. These data suggest that mediators other than those actually measured may play a significant role in the clinical late-phase reaction.
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In vitro effects of H1-antihistamines on histamine and PGD2 release from mast cells of human lung, tonsil, and skin.
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Mast cells from different anatomic sites differ in cytochemistry and response to various secretory stimuli. We have investigated whether responsiveness to the second-generation H1-receptor antagonists, which are important first-line drugs for the relief of symptoms in patients with chronic urticaria and allergic rhinoconjunctivitis, also differs according to the site of origin of mast cells. The effects of terfenadine, ketotifen, and cetirizine were therefore examined in relation to the IgE-dependent release of histamine and prostaglandin D2 (PGD2) from dispersed human lung, tonsil, and skin mast cells. Terfenadine had a biphasic effect on lung and skin mast cells: at low concentrations, a concentration-dependent inhibition of histamine release from lung and skin mast cells was observed, whereas at higher concentrations the drug stimulated mediator release. Even at a high concentration, terfenadine inhibited mediator release from tonsil mast cells. Ketotifen had low potency as an inhibitor of mediator release from lung and tonsil mast cells. In skin mast cells, no inhibition of mediator release was observed below 1.0 microM, and above that concentration it induced mediator release. Cetirizine, a much less lipophilic drug than the others tested, did not induce mediator release from mast cells even at concentrations up to 100 microM. This drug showed concentration-dependent inhibition of IgE-dependent mediator release from lung and tonsil mast cells only. Our results show that human mast cells are heterogeneous with respect to modulation of mediator release by these H1-antihistamines. In particular, differences were observed between skin mast cells and those dispersed from lung and tonsils.
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