Dose Of Ketotifen Research Articles

Survey on synergism effect of ketotifen in combination with pyrimethamine in treatment of acute murine toxoplasmosis

BackgroundStandard treatment of toxoplasmosis is accompanied by severe side effects and low tolerability; accordingly, alternative medicines are critically needed. Ketotifen (KET) as a cell membrane stabilizer could be an appropriate inhibitor of Toxoplasma gondii (T. gondii) parasite entrance into the host cells. Therefore, the focus of current study is characterization of the anti-Toxoplasma activity of KET in the acute phase of toxoplasmosis in murine model as pre-treatment and post-treatment (before and after infection with RH strain). KET was used intraperitoneally both individually (2 and 3 mg/kg/day) and in combination with pyrimethamine (PYR) (50 mg/kg/day). One week after the post infection, DNA was extracted from brain biopsies samples. Parasite load was calculated using Quantitative-PCR (Q-PCR) in a triplicate reaction for each DNA with the target for at RE (a 529 bp repeat element) gene.ResultsA significant difference between KET and control groups was observed (P < 0.001) in the pre-treatment and post-treatment groups. Both KET and the combination of KET and PYR showed a reduction in the parasite load in brain through the acute phase of the infection. 2 mg/kg/day dose of KET resulted in higher anti-Toxoplasma activity (15,698 parasites/ml) compared to 3 mg/kg/day dose of KET (72,898 parasites/ml) in brain in the pre-treatment group. In addition, KET combined with PYR significantly decreased the parasite load in the post-treatment group.ConclusionsOur results indicated that KET has both prophylactic and therapeutic effects on acute phases of the disease.

Impact of caffeine on weight changes due to ketotifen administration.

Prescription of ketotifen as an effective antihistamine in asthma and allergic conditions is associated with side effect of weight gain. Caffeine is an agent which increases thermogenesis and improves energy expenditure and also effective in asthma. The aim of current study was to evaluate caffeine impact in reducing weight gain side effect of ketotifen. Male mice at the weight limit of 20-30 gr in 8 groups were randomly chosen and injected following drug dosages for 45 days intraperitoneally: control group (normal saline 10 ml/kg), three groups of ketotifen (4, 8, 16 mg/kg), three groups of caffeine (4, 8, 16 mg/kg) and one group of ketotifen (4 mg/kg) in combination with caffeine (4 mg/kg). Weight changes have been recorded and assessed every 3 days for 45 days. The results showed that in all dosages of the two drugs, significant weight loss occurred in comparison with the control group. The effect of caffeine on weight loss according to our results, matches with human studies, while ketotifen contradictory to our assumption, resulted in weight loss which probably was related to the difference in metabolic pathways in mice and humans, or maybe the used doses of ketotifen in this study were insufficient to reduce TNF-α production or influence in serotonin release and be effective on appetite or weight gain.

Effects of low dose of ketotifen and chloroquine combination on the infrastructure of chloroquine resistant strain of Plasmodium yoelii

46 inbred NIH mice were infected by chloroquine resistant strain of Plasmodium yoelii. The ultrastructure changes were observed under the administration of ketotifen(10mg·kg−1·d−1) and chloroquine(10mg·kg−1·d−1) combination and one after another respectively. The effect of taking ketotifen and chloroquine combination showed that parasites died rapidly with a few of intermittent membranes and vacuoles. The effect of taking two kinds of drugs one after another showed that there were exceedingly rich membranes, concentric arrangement structures similar to rough endo-reticulum and conspiciously blocking of the formation of food vacuoles.

Effect of ketotifen on antigen-induced interleukin 2 (IL-2) responsiveness in lymphocytes from patients with atopic dermatitis and/or bronchial asthma

We tested the effect of Ketotifen (4-(1-methyl-4-piperidylidene)-4H-benzo[4,5] cyclohepta[1,2-b]thiophen-10(9H)-one hydrogen (fumarate) on the induction of allergen-induced IL-2 responsiveness in lymphocytes from patients with atopic dermatitis and/or bronchial asthma. Ovalbumin (OVA)- and/or Dermatophagoides farinae(Df)-induced IL-2-responsiveness was increased in almost all patients (1–15 years old) before Ketotifen treatment. Two to 12 months administration of Ketotifen (0.06 mg/kg/day) decreased activity of the response in 7 out of 9 cases corresponding to improvement of clinical symptoms. In in-vitro studies, antigen presenting cells (adherent cells) from the patient pretreated with 5, 50 and 500 ng/ml doses of Ketotifen for 12 h failed to present OVA or Df antigen to T-cells for induction of IL-2 responsiveness. Antigen-pulsed adherent cells also failed to induce the response of the T-cells pretreated with 50 and 500 ng/ml doses of Ketotifen but not with a 5 ng/ml dose. A 50 ng/ml dose of Ketotifen did not affect T-cells for induction of the response. In contrast, the treated adherent cells are capable of presenting PPD antigen of Con A for the induced response. The combined data indicate that induction of IL-2 responsiveness of peripheral blood lymphocytes on stimulation with nominal antigen may reflect an immune response to allergen in patients with allergy and a weak immunosuppressive effect of Ketotifen seems to block the response in the pathogenic process of allergic diseases.

Ketotifen treatment of adverse reactions to foods: clinical and immunological effects.

Fifteen patients with cutaneous signs and symptoms caused by adverse reactions to foods were treated in an open trial with ketotifen for 4 to 6 weeks. Seven subjects were allergic and 8 had food intolerance. Each patient was treated with a single dose of ketotifen daily: 2 mg half an hour before going to sleep. Clinical improvement was achieved in 6 out of 7 allergic patients and in 6 out of 8 patients with food intolerance. Since several drugs have been demonstrated to have an influence on immune response, the in vitro effects of ketotifen on some immunological parameters were also studied. Ketotifen showed a significant inhibitory effect on autologous mixed lymphocyte reaction responsiveness.

Further studies on the distinctive sleep‐wakefulness profiles of antihistamines (astemizole, ketotifen, terfenadine) in dogs

AbstractThe effects of the antihistamines astemizole, ketotifen, and terfenadine, given orally at the dose of 10 mg/kg, were investigated on 16‐hr sleep‐wakefulness patterns in dogs. As determined in the Ascaris allergy test in dogs, this dose had marked antihistaminic activity for at least the total duration of the recording. Using a computerized on‐line analysis and automatic sleep classification, a differentiation was made between wakefulness, transition to sleep, slow‐wave sleep, and REM (or paradoxical) sleep. Astemizole did not significantly change sleep‐wakefulness patterns. Ketotifen significantly increased slow‐wave sleep and significantly decreased REM sleep. Terfenadine significantly decreased wakefulness and significantly increased both slow‐wave sleep and REM sleep. With both ketotifen and terfenadine, REM latency was prolonged. Two different mechanisms appear to be involved in the REM sleep effects seen with terfenadine: an early REM sleep suppressant effect and a late but large REM sleep‐enhancing effect. This study shows central effects of terfenadine that are not completely typical for H1 antagonists but which are very pronounced at a dose producing much weaker peripheral antihistamine activity than the same dose of ketotifen and astemizole.

β-adrenergic tachyphylaxis in the rat and its reversal and prevention by ketotifen

A strong, long-lasting and reproducible tachyphylaxis was produced in rats by implantation of osmotic minipumps delivering isoprenaline continously. The degree of tachyphylaxis was determined by measuring the inhibitory effect of isoprenaline on the passive cutaneous anaphylaxis (PCA). One dose of ketotifen given 1 h before the PCA test reversed this in vivo tachyphylaxis, as did dexamethasone given 24 h earlier. Implantation of a second minipump containg ketotifen prevented the development of tachphylaxis. Weak tachphylaxis was induced in guinea-pig trachea in vitro by incubation with a high concentration of isoprenaline, the effect being estimated by measuring the relaxation of carbachol-contracted trachea. Ketotifen partially restored the sensitivity of the trachea but this was considered to be a direct potentiation of isoprenaline effects rather than a reversal of tachphylaxis since the same effect was seen in non-pretreated trachea. It is thought that the reversal of experimental β-adrenergic tachyphylaxis by ketotifen could have implications for its use in the prophylactic treatment of asthma.