Subcutaneous brompheniramine for cutaneous analgesia in rats.

Brompheniramine as an antihistamine blocked sodium channels, and local anesthetics by blocking sodium channels produced the local anesthetic effects. The authors aimed to assess local anesthetic quality and duration of brompheniramine when compared to the local anesthetic mepivacaine. After rats were shaved and injected subcutaneously on the dorsal skin, the panniculus reflex, induced via applying a noxious pinprick to the skin (injected area), was scored. The dose-response curve and nociceptive block duration of brompheniramine were constructed and compared with mepivacaine. The cutaneous analgesic effects in both brompheniramine and mepivacaine groups were concentration-dependent. On the basis of the amount required to produce a 50% block effect (ED50, 50% effective dose), the drug's potency was brompheniramine (0.89 [0.82-0.96] µmol) better than mepivacaine (2.45 [2.17-2.76] µmol) (P < 0.01). Full recovery time of brompheniramine was more prolonged than mepivacaine's (P < 0.01) on infiltrative cutaneous analgesia when comparing ED25s, ED50s and ED75s. Our preclinical data demonstrated that subcutaneous brompheniramine induces dose-relatedly analgesic effects, and brompheniramine induces prolonged analgesic duration when compared with mepivacaine. Brompheniramine also provokes better cutaneous analgesia than mepivacaine.

Brompheniramine and Chlorpheniramine Pharmacokinetics Following Single-Dose Oral Administration in Children Aged 2 to 17 Years.

Two pediatric studies characterized brompheniramine and chlorpheniramine pharmacokinetics in a total of 72 subjects, aged 2 to 17 years. A single age-/weight-based oral dose, ranging from 1 to 4 mg, was administered with 2 to 6 oz of water at least 2 hours after a light breakfast. Plasma samples were obtained before and for 72 hours after dosing and analyzed using high-pressure liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated using noncompartmental methods; relationships with age were assessed using linear regression. Results indicated that for brompheniramine and chlorpheniramine, Cmax was similar across age groups, although it tended to occur earlier in the youngest group. AUC was ∼15% to 30% higher in the oldest age group. As expected, CLo and Vz /F increased with age; however, following allometric scaling, no age-related differences existed. Because the increase with age for both parameters was similar, no age-related differences in t1/2,z existed (∼15 hours). Overall, the single doses were well tolerated. Sedation was the most common reported AE and appeared to be more prevalent in the 2- to 5-year-old group. Overall, these results indicate that an age/weight dosing nomogram using a 4-fold range of doses achieves similar Cmax and AUC.

Nimesulide-induced fixed drug eruption.

BACKGROUND: Nimesulide is a cyclooxygenase (COX) inhibitor with a high degree of selectivity to COX-2. It is a widely used and well tolerated nonsteroidal antiinflammatory drug that also has analgesic and antipyretic properties. The most frequently reported side effects concern the gastrointestinal tract. Pruritus and skin rash are the most common cutaneous adverse reactions. There are only eight cases of fixed drug eruptions due to nimesulide, described in the literature. CASE REPORT: The authors report a case of a patient with a history of antihistamine hypersensitivity who developed a bullous form of pigmented fixed drug eruption after nimesulide ingestion. Patch tests performed on residual skin lesion were positive to nimesulide, confirming that this was the culprit drug. CONCLUSIONS: Fixed drug eruptions are common cutaneous drug reactions, often misdiagnosed. A detailed anamnesis and physical examination are the key to suspect this condition.

Food-associated drinking in pygmy goats: importance of histamine receptors.

The combined effect of the histamine receptor antagonists Dexbrompheniramine (DXB: H1-receptor antagonist) and Cimetidine (C: H2-receptor antagonist) on food and water intake was investigated in pygmy goats. DXB (1 mg/kg BW0.75) and C (16 mg/kg BW0.75) were injected together intraperitoneally (i.p.). Cumulative food and water intake, as well as meal and draft pattern, were recorded. DXB and C significantly reduced cumulative water intake, whereas cumulative food intake did not change. Water to food ratio was also significantly diminished. Draft frequency and the percentage of drafts associated with meals were significantly reduced during the 6 h post injection, while meal frequency and meal size did not change during this period. The results show that blockade of the H1- and H2-histamine receptors attenuates the association between water and food intake in pygmy goats. Therefore, mechanisms responsible for meal-associated drinking seem to depend upon activation of histamine receptors.

A double-blind, placebo-controlled trial of decongestant-antihistamine for the treatment of sinusitis in children.

We studied the effectiveness of nasal decongestant-antihistamine in treating acute sinusitis in children. All subjects received oral amoxicillin for 14 days. Subjects randomized to the decongestant-antihistamine group received nasal oxymetazolone and oral syrup containing brompheniramine and phenylpropanolamine. Controls received placebo nasal saline and oral syrup. In both groups symptoms resolved quickly, and radiographs improved significantly. Responses to treatment were similar between the two groups. Water's radiographs of the maxillary sinuses proved reliable in the assessment of the degree of sinus involvement. We conclude that decongestant-antihistamine need not be given to the child with acute maxillary sinusitis.

Effect of food on bioavailability of pseudoephedrine and brompheniramine administered from a gastrointestinal therapeutic system.

The purpose of this study was to determine how a high-fat meal affects the delivery and absorption of pseudoephedrine and brompheniramine maleate when delivered from a gastrointestinal therapeutic system (GITS). This study was a randomized, complete crossover trial with 12 healthy male volunteers who were given single doses of the 24-h GITS under fed and fasted conditions. Pharmacokinetic parameters for both drugs were comparable between fed and fasted treatments, except for a shorter time to maximum concentration of pseudoephedrine for fed subjects (p = 0.002). Bioavailability of pseudoephedrine was 91% for fed relative to fasted treatment; for brompheniramine it was 89%. These results indicate that codelivery of the two drugs from the GITS is reliable and prolonged, and that the resulting absorption of pseudoephedrine and brompheniramine is minimally affected by food.

Cough and the common cold.

To determine whether the cough of the common cold arises from upper respiratory stimuli and whether antihistamine-decongestant therapy is an effective treatment for this cough, we prospectively evaluated volunteers with uncomplicated common colds in a randomized, double-blind, placebo-controlled study. After completing a standardized questionnaire and undergoing a physical examination, throat-culturing, and pulmonary function testing, subjects took the active drug or identical-appearing placebo for 7 days while they kept a diary in which they ranked the severity of 17 symptoms for 14 days. Pulmonary function testing was repeated, on average, on Days 4, 8, and 14. Forty-six percent of the variation in cough severity could be explained by throat-clearing and 47% of the variation in throat-clearing severity by postnasal drip. FIF50%, the only physiologic parameter that significantly correlated with cough, rose as cough severity fell. Antihistamine-decongestant therapy reduced postnasal drip and significantly decreased the severity of cough, nasal obstruction, nasal discharge, and throat-clearing during the first few days of the common cold. In addition, cough was 20 to 30% less prevalent in the active drug group within 3 days of starting therapy. We conclude that the cough of the common cold arose from upper respiratory tract stimuli and that cough and other cardinal symptoms of the common cold were reduced with antihistamine-decongestant therapy when these symptoms were at their worst.

Nasal pharmacodynamics of brompheniramine in perennial rhinitis.

This study evaluated the relationship between brompheniramine maleate and changes in nasal reactivity. Ten subjects with moderate-to-severe perennial rhinitis took brompheniramine for seven days using either a standard formulation or sustained-release preparation. Nasal aerodynamics and response to histamine were assessed at the end of the week. Despite varying doses of brompheniramine maleate (12 to 32 mg/d), there was no significant difference in nasal reactivity to histamine or in changes of nasal airflow, indicating that low doses of brompheniramine are highly effective in blocking histamine, receptors in the nasal mucosa.

Steady-state bioavailability of dexbrompheniramine and pseudoephedrine from a repeat-action combination tablet.

The steady-state bioavailabilities of dexbrompheniramine and pseudoephedrine were evaluated following multiple-dose administrations of a repeat-action combination tablet containing 6 mg of dexbrompheniramine maleate with 120 mg of pseudoephedrine sulfate every 12 h for 7 d compared with reference standards. The reference standards used in this study were concomitant administration of conventional 2-mg dexbrompheniramine maleate tablets every 4 h and 120-mg pseudoephedrine sulfate repeat-action tablets every 12 h, each for 7 d. Twelve healthy adult male volunteers completed this randomized two-way crossover study. Blood samples for subsequent assay were obtained at frequent time intervals throughout each 7-d dosing phase. Sensitive and specific gas-liquid chromatographic methods were used for the determination of dexbrompheniramine and pseudoephedrine in plasma. Based on the plasma levels, the times to reach steady state were determined. In addition, the major bioavailability parameters (Cmin, Cmax, tmax, and AUC) for days 6 and 7 of dosing were determined and statistically evaluated. The results of this study demonstrate that, at steady state, the repeat-action combination tablet and concomitant administration of the reference standards are bioequivalent.

A placebo-controlled comparative study of sustained-release brompheniramine maleate against clemastine fumarate in the treatment of chronic urticaria.

A partially-blind, three-way crossover study was carried out in 24 patients suffering from chronic urticaria to compare the efficacy and tolerance of brompheniramine maleate with that of clemastine fumarate. Patients received 4-week courses of treatment with 1 tablet twice daily of either 12 mg brompheniramine, 1 mg clemastine or placebo, in random order. Assessments were made by the physician of the patients' condition on entry and of response to treatment at the end of each 2-week period throughout the 12-week study period. At the end of the trial, patients were asked to state their preference, if any, for the different treatments. The results showed that both antihistamines were significantly effective compared to placebo and that at the dosage used brompheniramine was considered significantly better than clemastine in long-term control. Drowsiness was experienced by 4 patients whilst taking brompheniramine compared to 3 patients whilst taking clemastine. One patient experienced anorexia and vomiting with brompheniramine and 4 patients developed gastro-intestinal upsets whilst taking the placebo.

[Effect of chronic use of antidepressants on the state of benzodiazepine receptors in the mouse brain]. / Vliianie khronicheskogo primeneniia antidepressantov na sostoianie benzodiazepinovykh retseptorov golovnogo mozga myshi.

A study was made of the effect of a two-week administration of chlorimipramine, zimelidine and a morpholine derivative on benzodiazepine receptors of the mouse brain. The animals which received antidepressants demonstrated a significant increase in the binding sites of 3H-flunitrazepam without any changes in the dissociation constant as compared to control. The data on the evoked aggressiveness and latency of tonic corasole convulsions in the antidepressant-treated animals support the functional importance of the discovered changes in benzodiazepine receptors.

An antihistamine/decongestant formulation ('Disophrol' Syrup) for relief of symptoms in children with seasonal rhinitis.

An open study was carried out in 30 children with seasonal allergic rhinitis to evaluate the efficacy and tolerance of treatment with a dexbrompheniramine maleate (1.5 mg/5 ml) and pseudoephedrine sulphate (30 mg/5 ml) syrup formulation ('Disophrol' Syrup). Each patient was given 2.5 to 5 ml 4-times daily during the 14-day study period. Relief from signs and symptoms associated with seasonal rhinitis was evaluated on Days 7 and 14 of therapy. By Day 7, 5 patients were considered cured, 22 showed marked improvement and 3 patients had improved. At the Day 14 evaluation, 27 patients had complete clearing of signs and symptoms, 2 patients showed a marked improvement while the remaining patient was considered a treatment failure. Body weight and vital signs remained unaffected. Incidence of adverse reactions was limited to one occurrence of extreme fatigue, which did not necessitate termination of therapy.

The pharmacokinetics and antihistaminic effects of brompheniramine.

We studied the pharmacokinetics and antihistaminic effect of brompheniramine in seven normal adults. The mean peak serum brompheniramine concentration of 11.6 +/- 3.0 ng/ml occurred at a mean time of 3.1 +/- 1.1 hr. The mean serum half-life value was 24.9 +/- 9.3 hr, the mean clearance rate was 6.0 +/- 2.3 ml/min/kg, and the mean volume of distribution was 11.7 +/- 3.1 L/kg. The mean wheal size was significantly suppressed (p less than or equal to 0.1) at 3, 6, and 9 hr after the brompheniramine dose when mean concentrations ranged from 10.2 +/- 2.9 to 7.0 +/- 2.2 ng/ml. Significant suppression (p less than or equal to 0.05) of mean flare size was found from 3 to 48 hr after the brompheniramine dose, when mean concentrations ranged from 10.2 +/- 2.9 to 2.5 +/- 0.6 nl/ml. The mean pruritus score was significantly suppressed at 9 and 12 hr (p less than or equal to 0.1) and at 24 hr (p less than or equal to 0.05). Brompheniramine had a long half-life and large volume of distribution in normal adults. It also had a prolonged antihistaminic effect in the skin as evidenced by suppression of the wheal and flare response to histamine and by suppression of pruritus.

Differences in performance impairment due to brompheniramine maleate as a function of the sustained-release system.

1 study examined whether different sustained release systems would cause variation in the effect of an antihistamine, brompheniramine maleate 10 mg, upon mood and psychomotor performance. Two commercial preparations were examined, one giving linear release (LR) of the drug over time, the other releasing the drug in a non-linear fashion (NLR). 2 Thirty-six males were allocated to four separate groups receiving either the drug with LR, drug with NLR, placebo or drug-free control. Single dosage of the drug occurred at 08.30 h and subjects completed mood inventories and performed serial choice reaction time and visual search tasks at 1 h, 2.75 h, 5.5 h and 7.25 h post dosage. 3 The NLR system significantly increased feelings of unco-ordination at 2.75 h and significantly slowed reaction time at both 2.75 and 5.5 h post dosage. The LR system significantly slowed reaction time only at 5.5 h but increased pausing in serial choice performance at that time. Neither system impaired visual search. 4 Results suggest that two preparations having identical active constituents may vary in their effects on psychomotor performance and mood as a function of their sustained release systems. A system giving linear release of the drug can reduce the early post-dosage performance decrement associated with a non-linear release system.

Oral vasoconstrictors in perennial non-allergic rhinitis.

Nasal airway resistance and nasal symptoms were evaluated in patients with perennial non-allergic rhinitis before and after vasoconstrictory drugs and placebo taken orally. The patients were partly selected; those suffering mainly from nasal obstruction being tested. Phenylpropanolamine (PPA) in a dose of 100 mg in a sustained-release preparation clearly decreased the nasal airway resistance measured rhinomanometrically. PPA in a dose of 50 mg and combined with an antihistamine had no obvious decongesting effect. Placebo and dihydroergotamine (DHE) in a dose of 5 mg did not decrease the nasal airway resistance PPA (100 mg) and the combined preparation containing PPA in the lower dose (50 mg) taken twice a day in a cross-over, double-blind study significantly reduced nasal obstruction, secretion, and sneezing compared with placebo. Side effects of PPA are discussed.

Disophrol syrup versus Rinomar syrup in the treatment of allergic rhinitis in children.

In this single-blind study, the efficacy and safety of Disophrol Syrup was compared to Rinomar Syrup in seventy-eight paediatric patients with seasonal allergic rhinitis. Patients took 5-10 ml of the randomly assigned medication three to four times daily for a 2-week period. Severity of nasal obstruction, nasal secretion and mucosal swelling was graded and patient response to each week of therapy evaluated. An overall favourable response to Disophrol Syrup was observed in thirty-one out of thirty-five (89%) patients and in thirty out of thirty-five (86%) patients in the Rinomar group. No statistically significant difference in patient response to therapy between treatment groups was noted and no mentionable adverse reactions were reported.

Zimelidine: comparison of different dosage regimes in general practice.

Various studies have demonstrated that depressive symptoms are a frequent and important problem in general practice. Zimelidine has been shown to have effective antidepressant activity. A controlled double-blind trial was set up to compare the efficacy and side effects of zimelidine when given as a single daily dose (200 mg night or morning) and when given as a divided dose (100 mg b.d.). These three dosage schedules were studied. The trial was conducted among patients attending their general practitioners and suffering from a depressive disorder. Using one of the three dosage schedules, these patients were treated with zimelidine for a minimum period of 6 weeks. Symptom severity was measured by means of the Hamilton Rating Scale for Depression and the side effects assessed using an adverse event record and a symptom checklist. The findings are discussed.

Pharmacokinetics of zimelidine in humans--plasma levels and urinary excretion of zimelidine and norzimelidine after intravenous and oral administration of zimelidine.

Five healthy adults were administered zimelidine orally (150 mg) and by intravenous infusion (20 mg) in a crossover design. Blood and urine samples were collected for a period of 28 hours after dosing and the concentrations of zimelidine and norzimelidine determined. There was no significant difference in terminal phase half-life of zimelidine after oral (4.7 h +/- 1.3 SD) or intravenous dosing (5.1 h +/- 0.7 SD). An average of 50% of the ingested oral dose reached the systemic circulation. Excretion of unchanged zimelidine in urine was on average 1.26% of the intravenous dose. It appears that zimelidine is completely absorbed from the gastrointestinal tract and "first-pass metabolism" in the liver reduces the bioavailability to 50%. The mean plasma half-life for norzimelidine was 22.8 h. The area under the plasma concentration time curve for norzimelidine after oral administration was 92% of that after intravenous administration. The plasma concentration of both zimelidine and norzimelidine are predicted to approach steady-state within 3--5 days.