Pharmacokinetics and antipruritic effects of hydroxyzine in children with atopic dermatitis

doi:10.1016/S0022-3476(84)80608-3

The Journal of Pediatrics

Volume 104, Issue 1, January 1984, Pages 123-127

https://doi.org/10.1016/S0022-3476(84)80608-3 Get rights and content

We studied the pharmacokinetics and antipruritic effects of hydroxyzine hydrochloride in 12 children, mean age 6.1±4.6 years, with severe atopic dermatitis. After a single 0.7 mg/kg orally administered dose of the drug, the mean peak serum hydroxyzine concentration of 47.4±17.3 ng/ml occurred at a mean time of 2.0±0.9 hours. The mean elimination half-life was 7.1±2.3 hours, the mean clearance rate was 32.08±11.05 ml/min/kg, and the mean apparent volume of distribution was 18.5±8.6 L/kg. The elimination half-life increased with increasing age (r=0.83). Pruritus was significantly suppressed from 1 to 24 hours after the administration of the dose, with greater than 85% suppression from 2 to 12 hours. The only adverse effect reported was sedation. In a subsequent double-blind, crossover, multiple-dose study of 2 weeks' duration, hydroxyzine 0.7 mg/kg three times daily was as effective as hydroxyzine 1.4 mg/kg three times daily in relieving pruritus and promoting resolution of the skin lesions. The 0.7 mg/kg tid dose caused significantly less sedation than the 1.4 mg/kg tid dose.

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This study reported no serious side effects or sedation among patients. Moreover, this dose range was effective as antipruritic in atopic dermatitis patients [44]. In order to investigate the antipruritic eﬀect of the transdermal gel (F4) of HHCL-SLNs in atopic dermatitis, such as DNCB induced lesions.
Hydroxyzine HCL (HHCL) is an antihistamine, used for the treatment of allergic skin conditions. The purpose of this study was to achieve a dual phase drug delivery rate across the intact skin, to enhance HHCL permeation through the stratum corneum, to assess the peripheral H₁-antihistaminic activity and the extent to which HHCL was systemically absorbed from transdermal gel loaded with solid lipid nanoparticles (SLNs), as well as to avoid its extreme bitterness. According to 2³ factorial design, eight formulations of HHCL-SLNs were prepared by the double emulsification method. Lipid type (X_A), surfactant concentration (X_B) and co-surfactant concentration (X_C) were the independent variables. All formulations were characterized for their surface morphology, particle size, entrapment efficiency and in-vitro drug release study. The optimized formula that provides greater desirability was then incorporated into the transdermal gel. In addition, the efficacy of the developed gel was tested in-vivo using 2,4-Dinitrochlorobenzene induced atopic dermatitis as lesion model in mice. F4 showed an average diameter 111 nm ± 0.03, zeta potential − 30 MV ± 2.4 and EE 75.2% ± 4.4. TEM images showed spherical, smooth morphology with uniform particles distribution. In-vivo study demonstrated potent antipruritic efficacy of transdermal gel in atopic dermatitis such as induced lesions compared to HHCL gel. Hence, HHCL solid lipid nanoparticles transdermal gel may be considered as potential for delivery of HHCL and alternatively to traditional oral use.
Crisis in the Emergency Department: The Evaluation and Management of Acute Agitation in Children and Adolescents
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Effects of Lecythis pisonis Camb. (Lecythidaceae) in a mouse model of pruritus
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Four histamine receptors subtypes have been identified to date (Rossbach et al., 2011), and histamine receptor subtype I (H1R) has been most extensively studied in the context of histamine-induced itch. In fact, H1R blockers (antihistamines) are widely used to manage and relieve itch symptoms (Simons et al., 1984). However neither type of antihistaminics offers sufficient relief of most pruritus, such as topic dermatitis, chronic cholestase and to date no drug, effective in the full spectrum of pruritus, has been described.
Lecythis pisonis Camb. (Lecythidaceae), is popularly known as “Sapucaia”. In traditional medicine, leaves are used for the treatment of pruritus.
The present study is aimed to investigate the antipruritic effect of the ethanol extract from leaves of Lecythis pisonis (LPEE), fractions (hexane-LPHF, ether-LPEF and ethyl acetate-LPEAF) and mixture of triterpenes [ursolic and oleanolic acids (MT)] in mice and rats.
The LPEE, LPHF, LPEF, LPEAF and MT were evaluated on scratching behavior induced by compound 48/80 in mice. In addition, LPEE, LPEF and MT were investigated on rat peritoneal mast cells degranulation induced by compound 48/80 (ex vivo study). The anti-inflammatory activity of LPEE and LPEF was investigated in rats using carrageenan-induced hind paw edema model. In the evaluation of the spontaneous motor activity, the LPEE was studied for its effect on spontaneous motor activity in an open-field test in mice.
The scratching behavior induced by compound 48/80 was significantly inhibited in mice pretreated with LPEE, LPHF, LPEF, LPEAF and MT. The suppressive effect of LPEE, LPEF and MT was only partially antagonized by naloxone. In addition, the compound 48/80-elicited degranulation of rat peritoneal mast cells was also markedly reduced in animals pretreated with LPEE, LPEF and MT. In the anti-inflammatory test, LPEE decreased the paw edema at the third hour after carrageenan (Carr) administration. Moreover, LPEF also was able to inhibit the oedematogenic response evoked by carr at all analysed time points. In the open-field test, LPEE-pretreated mice showed no impairment of spontaneous locomotion. Furthermore, the LPEE demonstrated no overt toxicity up to an oral dose of 2 g/kg in an acute toxicity assay.
These results clearly indicate the antipruritic effects of Lecythis pisonis leaves and suggest that this effect may be related to a stabilizing action on mast cell membrane. Furthermore, these data support the traditional use of this plant against cutaneous pruritus.
Hydroxyzine
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Hydroxyzine, a piperazine derivative, is a competitive antagonist of histamine H₁-receptors. Hydroxyzine has antiemetic and sedative effects that are thought to be mediated by its actions in brain. Hydroxyzine is used for the management of anxiety associated with psychoneuroses, of pruritus secondary to allergic conditions such as chronic urticaria or atopic or contact dermatoses, and in histamine-mediated pruritus. In addition, it is used for its sedative effects before and after general anesthesia. Hydroxyzine is the most efficacious and longest acting antihistamine in suppressing the wheal and flare response to histamine …
Levocetirizine: Pharmacokinetics and pharmacodynamics in children age 6 to 11 years
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Citation Excerpt :
In pharmacokinetic and pharmacodynamic studies of H1-antihistamines, although outcome measures such as blood tests and skin tests are highly objective, they are inherently invasive, and the studies therefore present unique challenges in children.2,4 Study designs do not usually involve a placebo control,7-20 not only because of ethical constraints and parental concerns about the use of placebo, but also because a potent H1-antihistamine suppresses wheals and flares by up to 100%,5,6,12,13 thus making it difficult to maintain double-masked observations and measurements. The objective, standardized, histamine-induced wheal-and-flare bioassay is useful for studying the onset, amount, and duration of activity of H1-antihistamines.
The pharmacokinetics and pharmacodynamics of medications may differ between children and adults, necessitating different dose regimens for different age groups. Levocetirizine, the active enantiomer of cetirizine, is used in the treatment of allergic rhinitis and chronic urticaria in Europe. Its pharmacokinetics and pharmacodynamics have not yet been studied prospectively in school-age children.
This study was performed to investigate levocetirizine pharmacokinetic disposition and pharmacodynamics in relation to skin reactivity to histamine in children aged 6 to 11 years.
Blood samples were obtained at predose baseline and at defined intervals up to and including 28 hours after a 5-mg levocetirizine dose. Concurrently, epicutaneous tests with histamine phosphate, 1 mg/mL, were performed. Wheals and flares were traced at 10 minutes, and the areas were measured with a computerized digitizing system.
In children aged 8.6 ± 0.4 years (± SEM), the peak levocetirizine concentration was 450 ± 37 ng/mL, and the time at which peak concentrations occurred was 1.2 ± 0.2 hours. The terminal elimination half-life was 5.7 ± 0.2 hours, the oral clearance was 0.82 ± 0.05 mL/min/kg, and the volume of distribution was 0.4 ± 0.02 L/kg. Compared with predose areas, the wheals and flares produced by histamine phosphate were significantly decreased from 1 to 28 hours, inclusive (P < .05). Mean maximum inhibition of wheals and flares occurred from 2 to 10 hours (97% ± 1%) and from 2 to 24 hours (93% ± 1%), respectively.
Levocetirizine had an onset of action within 1 hour and provided significant peripheral antihistaminic activity for 28 hours after a single dose. Once-daily dosing may be optimal in children aged 6 to 11 years, as it is in adults.
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²: Supported by Children's Hospital of Winnipeg Research Foundation, Inc.

¹: From the Section of Allergy and Clinical Immunology, Department of Pediatrics, Faculty of Medicine; Faculty of Pharmacy; and the Section of Dermatology, Department of Internal Medicine, Faculty of Medicine, University of Manitoba.

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Pharmacokinetics and antipruritic effects of hydroxyzine in children with atopic dermatitis2

J Allergy Clin Immunol

J Am Acad Dermatol

J Pharm Sci

Curr Ther Res

J Pharm Sci

Major Probl Dermatol

J Invest Dermatol

J Invest Dermatol

A comparison of the antipruritic efficacy of hydroxyzine and cyproheptadine in children with atopic dermatitis

Ann Allergy

Treatment of pruritus in allergic dermatoses: An evaluation of the relative efficacy of cyproheptadine and hydroxyzine

Curr Ther Res

Eczema (atopic dermatitis)