Aphthasol
Tardive dyskinesia and neurotransmitters: effects of sodium valproate, cyproheptadine, oxypertine, hydroxyzine pamoate and Ca-hopantenate on monoamine metabolites, cyclic nucleotides and gamma-aminobutyric acid in human cerebrospinal fluid.

Ogawa T, Nagao T, Kashiwabara K, Fujiwara Y, Harada T, Otsuki S.

Lumbar cerebrospinal fluid (CSF) homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), cyclic AMP (cAMP) and cyclic GMP (cGMP) were measured in chronic schizophrenics with tardive dyskinesia before and three weeks after the initial treatment with sodium valproate (VPA), cyproheptadine, oxypertine or hydroxyzine pamoate. HVA levels significantly decreased after the administration of VPA, cyproheptadine or oxypertine. Cyclic GMP levels significantly increased after the administration of VPA or cyproheptadine. Elevation of the cAMP level was observed after the administration of VPA, cyproheptadine or oxypertine. An elevation of the MHPG level was observed during oxypertine treatment and a reduction of the 5-HIAA level was observed during hydroxyzine pamoate treatment. Decreases in HVA and increases in cGMP levels during treatment might be indicative of normalization of the dopaminergic-cholinergic imbalance in the brain. Lumbar CSF HVA and gamma-aminobutyric acid (GABA) were also measured in patients with tardive dyskinesia before and eight weeks after Ca-hopantenate treatment. No significant changes were observed before or after this treatment. The hypothesis is discussed that the pathogenesis of tardive dyskinesia may involve functional disorders not only of the dopaminergic or cholinergic system but also of the norepinephrinergic, serotoninergic and GABA-ergic systems.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6085032&dopt=Abstract hydroxyzine Atarax



Aphthasol
The pharmacokinetics and antihistaminic of the H1 receptor antagonist hydroxyzine.

Simons FE, Simons KJ, Frith EM.

We studied the pharmacokinetics and the suppression of histamine-induced wheals, flares, and pruritus in the skin after administration of the histamine H1 antagonist hydroxyzine to seven healthy adults. After a single oral dose of hydroxyzine, 0.7 mg/kg (mean dose 39.0 +/- 5.4 mg), the mean maximum serum hydroxyzine concentration of 72.5 +/- 11.1 ng/ml occurred at a mean time of 2.1 +/- 0.4 hr. The mean elimination half-life calculated from the terminal linear portion of the serum hydroxyzine concentration vs. time curve was 20.0 +/- 4.1 hr. The mean clearance rate was 9.78 +/- 3.25 ml/min/kg and the mean volume of distribution was 16.0 +/- 3.0 L/kg. The single dose of hydroxyzine suppressed pruritus at the wheal and flare sites from 1 to 36 hr. Maximal suppression of the wheals was 80% and maximal suppression of the flares was 92%. Significant suppression of the wheals and flares persisted for 36 and 60 hr, respectively. Pharmacodynamic analysis of the wheal and flare suppression data and the mean serum hydroxyzine concentrations supports the prolonged terminal serum half-life value for the drug.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6141198&dopt=Abstract hydroxyzine Atarax



Aphthasol
Effect of hydroxyzine on the transport of etoposide in rat small intestine.

Kan WM, Liu YT, Hsiao CL, Shieh CY, Kuo JH, Huang JD, Su SF.

Department of Pharmacology, National Cheng Kung University, Medical College, Tainan 70101, Taiwan, ROC.

Etoposide, an anti-neoplastic agent and a substrate of P-glycoprotein (P-gp), exhibits variable oral bioavailability. P-gp, the multidrug resistance gene (mdr1) product, has been considered as an absorption barrier against intestinal drug absorption. Terfenadine, an antihistamine, has been shown to be a P-gp inhibitor. The current study was designed to assess the effect of hydroxyzine, an antihistamine, on the transport of etoposide in the small intestine. Everted rat gut sacs were used to determine the absorption and exsorption of etoposide under different conditions, as rhodamine 123 was chosen to evaluate the role of P-gp in the drug interaction. The results showed that the transport of etoposide was significantly increased from the luminal site to the serosal site in the jejunum by 2- and 4-fold after 90 min in the presence of hydroxyzine and quinidine, respectively. A similar trend was observed in the ileal sacs. This in vitro exsorption study also demonstrated that hydroxyzine could reduce the efflux of etoposide to the luminal site in either jejunum or ileum. The effect of hydroxyzine on the pharmacokinetics of etoposide differed by the in vivo route of administration, thus assuming clinical importance for chemotherapeutic treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11290874&dopt=Abstract hydroxyzine Atarax



Aphthasol
Analgesic efficacy and pharmacokinetic evaluation of meperidine and hydroxyzine, alone and in combination.

Stambaugh JE Jr, Lane C.

As part of a study to evaluate the analgesic efficacy of meperidine and hydroxyzine, alone and in combination, a double-blind complete crossover study of meperidine (50 mg IM), hydroxyzine (100 mg IM), meperidine (50 mg IM) plus hydroxyzine (100 mg IM), and saline placebo was conducted. Thirty patients with chronic moderate to severe pain due to metastatic cancer were evaluated as to pain relief following administration of all four study medications. All of the treatment groups showed statistically significant analgesic activity as compared to placebo. Hydroxyzine provided sustained pain relief to six hours, whereas meperidine produced analgesia up to two hours. The combination produced additive analgesia only during the first 2 hr. The pharmacokinetics of meperidine and hydroxyzine were compared to observed analgesia. Significant correlation between serum drug levels of meperidine and hydroxyzine and pain relief resulted and the serum levels of meperidine and hydroxyzine necessary for analgesia were calculated to be 0.10-0.15 mg/ml and 60-70 ng/ml; respectively. The observed analgesia of the meperidine/hydroxyzine combination was correlated with the analgesia of the individual agents and the limited additive analgesia observed with the addition of meperidine to hydroxyzine does not justify the added toxicity of the narcotic.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6199095&dopt=Abstract hydroxyzine Atarax



Aphthasol
The effect of clemastine and hydroxyzine on cutaneous histamine response in man.

Rihoux JP, Polderman J.

Histamine-induced cutaneous wheals were measured in five healthy volunteers 2, 4, 8 and 24 hours after per os administration of a single dose of clemastine 1 mg and hydroxyzine 25 mg. Clemastine produced a mean wheal suppression of 9%, 18% and 6%, while hydroxyzine produced a mean wheal suppression of 49%, 73%, 82% and 77%. This experiment demonstrates the potent and long-lasting anti-H1 effect of hydroxyzine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7141095&dopt=Abstract hydroxyzine Atarax