Aphthasol
Physicochemical stability of a preanesthetic mixture of hydroxyzine hydrochloride and atropine sulfate.

Beatrice MG, Stanaszek WF, Allen LV, Stanton GK, Covington TR.

The stability of a combination of hydroxyzine hydrochloride and atropine sulfate stored in syringes was studied. Syringes containing the two drugs were stored at 25 C and 3 C for ten days and analyzed at specific time intervals. Absorption spectra, chromatographic characteristics and pH were determined. Results showed the admixture to be stable for ten days at room temperature or under refrigeration. The technique used would probably not detect any significant degradation of atropine sulfate unless the reaction occurred with the hydroxyzine hydrochloride.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=242215&dopt=Abstract hydroxyzine Atarax



Aphthasol
Cimetidine increases the plasma concentration of hydroxyzine.

Salo OP, Kauppinen K, Mannisto PT.

The combination of hydroxyzine and cimetidine is reported to be more effective than hydroxyzine alone in chronic urticaria. The plasma concentration of hydroxyzine was studied in seven patients treated both with the hydroxyzine 25 mg t.i.d. and the combinations of hydroxyzine 25 mg and cimetidine 200 mg t.i.d. Hydroxyzine plasma concentrations were definitely higher during the combination treatment than during hydroxyzine alone. This may explain the effectiveness of the combination treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2430410&dopt=Abstract hydroxyzine Atarax



Aphthasol
The effect of chronic administration of hydroxyzine on hydroxyzine pharmacokinetics in dogs.

Simons KJ, Simons FE.

Subsensitivity to H1-receptor antagonists has been attributed to autoinduction of enzyme systems and increased clearance rates during chronic drug administration. We studied the changes in serum half-life values and clearance rates in dogs who were administered hydroxyzine, 0.7 mg/kg, intramuscularly, daily, for 150 days. Pharmacokinetic studies were performed on the first day of drug administration, and on days 30, 60, 90, 120, and 150. The mean serum half-life value on day 30, 60, and 120 was significantly longer (p less than 0.05) than that of 2.4 +/- 0.3 hours obtained on day 1. The mean clearance values obtained on days 30, 60, 90, 120, and 150 were significantly slower (p less than 0.05) than the value of 25.12 +/- 4.13 ml/min/kg obtained on day 1 but were not significantly different from each other. Mean serum hydroxyzine concentrations were often significantly higher on the later study days than on day 1. The mean apparent volume of distribution values obtained on days 30, 60, 90, 120, and 150 did not differ significantly from the value of 5.0 +/- 1.5 L/kg obtained on day 1. This study adds to the mounting evidence that subsensitivity to the effects of an H1-receptor antagonist is not due to autoinduction of enzyme systems, more rapid clearance of the drug, and lower concentrations of the drug in serum and tissue.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2884246&dopt=Abstract hydroxyzine Atarax



Aphthasol
Receptor effects of cetirizine.

Snyder SH, Snowman AM.

Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland.

First-generation H1-antagonist antihistamines such as hydroxyzine have a significant ability to cross the blood-brain barrier and cause sedation, which limits their usefulness in the treatment of allergic disorders. Cetirizine, a carboxylated metabolite of hydroxyzine, possesses the parent compound's antihistaminic activity but does not cause sedation. This lack of CNS effects may be due to cetirizine's greater selectivity or potency at H1 receptors in the brain, compared with its effects at the receptors involved in sedation, or it may result from the agent's relative exclusion from the CNS compartment. We compared cetirizine's activity at central H1 sites with the activity of hydroxyzine and terfenadine. We also compared the abilities of cetirizine and three other antihistamines to cross the blood-brain barrier. We found the drugs' potency at H1 receptors in the CNS to be similar to their activities in other tissues. However, their selectivity varied widely. Cetirizine, in fact, failed to bind at any of the receptors investigated except H1 sites, even at concentrations as high as 10 micron. Both hydroxyzine and D-chlorpheniramine crossed the blood-brain barrier in significant amounts. Terfenadine did so to a much lesser extent, and cetirizine passed into the CNS only half as readily as terfenadine. We suggest that cetirizine's reduced incidence of sedative side effects may stem partly from its selectivity for H1 receptors over sites involved in sedation, and partly from its relative exclusion from the CNS.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2892448&dopt=Abstract hydroxyzine Atarax



Aphthasol
Absence of amnesia induction in mice with hydroxyzine in comparison with three other minor tranquillizers.

Lenegre A, Avril I, Fromage S, Milinkevitch D, Porsolt RD.

ITEM-Labo, Kremlin-Bicetre, France.

Hydroxyzine (Atarax) was compared with three traditional anxiolytics (diazepam, meprobamate, triazolam) for potential amnesic activity in a step-through passive avoidance task in the mouse. The doses investigated were: hydroxyzine (4, 8 and 16 mg/kg); diazepam (0.25, 0.5 and 1 mg/kg); meprobamate (8, 16 and 32 mg/kg); triazolam (0.0015, 0.003 and 0.006 mg/kg). The doses investigated were chosen on the basis of prior experiments for not having sedative effects as measured in a photo-cell activity meter. All drugs were administered i.p. 30 min before the first trial of the passive avoidance task. The compounds were also investigated for eventual analgesic activity using the hot plate test. The results indicated that hydroxyzine up to sedative doses was devoid of amnesic activity, whereas clear signs of amnesia were induced by diazepam, meprobamate and triazolam at doses at least 8 times lower than those which reduced spontaneous motor activity. None of the compounds showed analgesic activity in the hot plate test suggesting that the signs of amnesia observed in the passive avoidance test were not due to reduced sensitivity to aversive stimulation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2900011&dopt=Abstract hydroxyzine Atarax