Chemical formula: C₂₁H₂₇ClN₂O₂ Molecular mass: 374.904 g/mol PubChem compound: 3658
Hydroxyzine is a first generation antihistamine, a piperazine derivative, with antimuscarinic and sedative properties.
Antihistamines act as competitive antagonists of histamine at H1 histamine receptors, thus inhibiting H1 receptor-mediated reactions, such as vasodilation, flare and itch reactions and sneezing.
First-generation H1 antagonists easily cross the blood-brain barrier, consequently producing well-documented sedative and anticholinergic effects.
First-generation antihistamines also have affinity for 5-HT receptors, alpha-adrenoreceptors, and muscarinic receptors. They also reduce cyclic GMP concentrations, increase atrioventricular nodal conduction, and inhibit activation of airway vagal afferent nerves.
Hydroxyzine has CNS depressant, anticholinergic, antispasmodic, and local anaesthetic activity, in addition to antihistaminic effects. The drug also has sedative, antiemetic and primary skeletal muscle relaxant activity.
An onset of sedative action of hydroxyzine is usually noted within 15 to 30 minutes after oral administration. Sedative effects persist for 4-6 hours following administration of a single dose.
Hydroxyzine suppresses the inflammatory response (wheal and flare reaction) and pruritus for up to 4 days after intradermal skin tests with allergens and histamine.
The therapeutic range for plasma hydroxyzine concentrations and the relationship of plasma concentration to clinical response or toxicity have not been established.
Hydroxyzine does not appear to increase gastric secretions or acidity, and usually has mild antisecretory effects.
It induces a calming effect in anxious tense adults. It is not a cortical depressant, but its action may be due to a suppression of activity in certain key regions of the subcortical area of the central nervous system.
Hydroxyzine is rapidly absorbed from the gastrointestinal tract.
After a single oral dose of hydroxyzine, 0.7 mg/kg (mean dose 39.0 +/- 5.4 mg) a mean maximum serum hydroxyzine concentration of 72.5 +/- 11.1 ng/ml has been shown to occur at a mean time of 2.1 +/- 0.4 hours.
Distribution of hydroxyzine into human body tissues and fluids has not been fully characterised. Following administration of hydroxyzine to animals, the drug is widely distributed into most body tissues and fluids with highest concentrations in the liver, lungs, spleen, kidneys, and adipose tissue. The drug is also distributed into bile in animals.
Hydroxyzine crosses the placental barrier which may lead to higher foetal than maternal concentrations.
Serum hydroxyzine concentrations do not necessarily reflect hydroxyzine tissue binding or distribution to skin receptor sites. Suppression of wheals, flares, and associated pruritis has been shown to persist even when serum hydroxyzine concentrations are low.
First-generation H1 antagonists easily cross the blood-brain barrier.
In a study group of healthy adults, the mean apparent volume of distribution has been found to be 16.0 +/- 3.0 L/kg.
Hydroxyzine is metabolised in the liver. Metabolites include cetirizine, which has antihistaminic activity. Cetirizine is formed from hydroxyzine via an oxidative biotransformation step.
An elimination half life of 20.0 +/- 4.1 hours and of 14.0 hours has been reported for hydroxyzine.
Total body clearance in adults is generally in the range of 5 to 12 ml/min/kg.
Hydroxyzine is eliminated by hepatic metabolism in humans. Cetirizine is mainly renally excreted.
The pharmacokinetics of hydroxyzine were studied in nine healthy elderly (mean age 69.5 +/- 3.7 years) subjects who ingested a single dose of hydroxyzine, 0.7 mg/kg (mean dose 49.0 +/- 6.7 mg). The mean serum elimination half life value of hydroxyzine in this elderly group was 29.3 +/- 10.1 hours (range 20.2 to 53.3 hours), which was significantly longer than that reported in younger subjects. The mean apparent volume of distribution of hydroxyzine in this elderly group was 22.5 +/- 6.3 L/kg (range 13.4 to 30.7L/kg), which was significantly larger than that reported to be found in young adults. Hydroxyzine has a long mean serum elimination half life value, a large volume of distribution and a prolonged pharmacodynamic effect (suppressive effect on wheal and flare response to histamine) in the elderly.
In the elderly a number of age-related biological and physiological changes may have an effect on the pharmacology of hydroxyzine and its metabolite, cetirizine. These changes may impact upon the pharmacologic functions of absorption, distribution, metabolism, excretion, and receptor sensitivity.
Dosage reduction may be appropriate in elderly patients.
The pharmacokinetics and antipruritic effects of hydroxyzine hydrochloride was studied in 12 children aged 1 to 14 years (mean age 6.1 +/- 4.6 years) with severe atopic dermatitis. The children were given a single orally administered dose of 0.7 mg/kg hydroxyzine. The mean peak serum concentration of 47.4 +/- 17.3 ng/ml occurred at a mean time of 2.0 +/- 0.9 hours. Terminal elimination half life was shorter in children than in adults, at a mean of 7.1 +/- 2.3 hours. This resulted from a larger clearance rate in children of 32.08 +/- 11.05 ml/min/kg. The elimination half-life values increased with increasing age. Half life values were approximately 4 hours in the 1 year old patients and 11 hours in the 14 year old patient.
Dosage should be adjusted in the paediatric population (see section 4.2 ‘Posology and Method of Administration’).
The pharmacokinetics and pharmacodynamics of hydroxyzine were studied in eight patients (mean age 53.4 +/- SD11.2 years) with primary biliary cirrhosis, given a single dose of 0.7 mg/kg (mean dose 43.9 +/- 6.6mg) hydroxyzine. All patients had abnormal liver biochemistry tests, all had biopsies compatible with primary biliary cirrhosis, and seven of eight had positive tests for antimitochondrial antibodies.
Hydroxyzine elimination was found to be impaired in patients with primary biliary cirrhosis. Mean peak hydroxyzine levels occurring at 2.3 +/- 0.7 hours were found to be 116.5 +/- 60.6 ng/ml, which was significantly higher than in other patient groups studied previously. Mean serum elimination half-life of hydroxyzine was 36.6 +/- 13.1 hours, which was significantly longer than in patients with normal hepatic function studied previously.
Dosage should be adjusted in patients with hepatic impairment.
The pharmacokinetics of hydroxyzine and of its active metabolite cetirizine were studied in patients with reduced kidney function. Eight healthy volunteers and eight patients with renal insufficiency received a single peroral dose of 50 mg hydroxyzine.
With regards to hydroxyzine, results showed moderate elevation of the average terminal half-life in the patients group (t1/2 14 vs. 23 h). The areas under the concentration-time curves (AUC) were 996 ng·h·ml-1 in the healthy volunteers group and 1621 ng·h·ml-1 in the patients group. For cetirizine, AUC measured 6036 ng·h·ml-1 in the healthy volunteers group and 31635 ng·h·ml-1 in the patients group. The study concluded that the reduced renal clearance of cetirizine may be of clinical importance in patients with renal failure.
Dosage should be adjusted in patients with renal impairment.
None stated.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
