lodoxamide-tromethamine and Asthma

A Nebulizer Chronolog, a portable device that houses a standard nebulizer canister, was used in a unique method to measure compliance with aerosolized medication. Each actuation is tabulated to within 4 minutes of the actual time of usage and can subsequently be displayed in a day-hour-minute format. Of the 19 patients studied for 12 weeks with a cromolyn-like agent, appropriate usage four times a day ranged from 4.3% to 94.8%. Underusage exceeded overusage and ranged from 5.2% to 95% of the study days. Younger subjects and male subjects were less likely to use the aerosol appropriately. Patients failed to write the truth in their diaries with overreporting of appropriate usage more than 50% of the times. Lack of compliance with aerosolized medication represents an important medical issue for the physicians caring for patients with asthma. The Nebulizer Chronolog elicits new insight into the disparity between reported and observed compliance.

Topics: Adolescent; Adult; Aerosols; Aged; Amino Acids; Asthma; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Nitriles; Oxamic Acid; Patient Compliance; Tromethamine

The efficacy of lodoxamide tromethamine in the treatment of asthma was studied in a 16-week double-blind, placebo-controlled study of 68 perennial allergic subjects with asthma. Patients received either lodoxamide tromethamine, 0.25 mg four times daily, or placebo, administered by metered-dose inhaler. Response to treatment was assessed by analyzing changes in asthma symptoms, inhaled bronchodilator requirements, and pulmonary function when compared to a 2-week baseline period. Patients treated with lodoxamide tromethamine demonstrated an improvement in daytime breathing difficulty, cough, sputum production, and sleep (p less than 0.01 to 0.05), but improvement was not significantly different from that demonstrated by placebo-treated patients. Patients from both treatment groups were able to reduce their inhaled bronchodilators (p less than 0.01), but again no significant difference was apparent between lodoxamide tromethamine and placebo treatment, nor were there any differences in peak expiratory flow rate or FEV1 between the two groups. Seven patients who received lodoxamide tromethamine withdrew because of a sensation of heat and gastrointestinal symptoms. Thus, although lodoxamide tromethamine possesses potent mast cell-stabilizing activity in vitro, we have failed to demonstrate any useful long-term effect in the treatment of mild allergic asthma.

Topics: Adolescent; Adult; Aerosols; Amino Acids; Asthma; Chronic Disease; Double-Blind Method; Female; Humans; Male; Middle Aged; Nitriles; Oxamic Acid; Respiratory Function Tests; Tromethamine

Highly purified species-specific grass pollen antigens were used for inhalation bronchial challenge in 12 patients with atopic asthma. This was found to result in reproducible experimental asthma. Lodoxamide tromethamine was administered by inhalation in two different doses, 0.01 mg and 0.1 mg, to each patient, in double-blind, random, placebo-controlled manner, 15 minutes before pollen inhalation. It was found to have a significant protective action at both doses (p less than 0.05), but it produced troublesome side effects at the higher dose of 0.1 mg.

Topics: Adult; Amino Acids; Asthma; Bronchial Provocation Tests; Clinical Trials as Topic; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Nitriles; Oxamic Acid; Poaceae; Pollen; Random Allocation; Tromethamine

The inhibition of immediate allergen-induced airflow obstruction by lodoxamide tromethamine (LT), a new drug with properties considered to be similar to those of sodium cromoglycate, was studied in twelve young asthmatic volunteers. Single aerosolized doses of 0 X 01 mg LT, 0 X 1 mg LT or placebo were administered by inhalation 15 min prior to allergen provocation at weekly intervals, in a double-blind random order study. Following inhalation of both doses of LT a significantly greater amount of allergen had to be administered to cause a 20% fall in the forced expiratory volume in one second (FEV1) from control levels than was the case following placebo pre-treatment (P less than 0 X 001). After single-dose inhalation of LT only minor unwanted effects were recorded; in particular a transient feeling of heat in the upper respiratory tract after inhalation of the higher dose of drug.

Topics: Administration, Intranasal; Adult; Allergens; Amino Acids; Asthma; Bronchial Provocation Tests; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Humans; Hypersensitivity, Immediate; Male; Nitriles; Oxamic Acid; Tromethamine

Lodoxamide tromethamine, a new cromolyn-like drug, was studied to determine its effectiveness and duration of action in preventing antigen-induced bronchospasm in 15 subjects with clinically stable extrinsic asthma. All subjects underwent antigen inhalation challenge 15 min after inhalation of an aerosolized solution of 0.1 mg of lodoxamide in saline or of saline solution alone (placebo) administered on separate days according to a double-blind, random-allocation protocol. Those subjects demonstrating a protective effect of lodoxamide subsequently underwent antigen inhalation challenges at various time intervals (2 to 8 hr) after lodoxamide treatment. Thirteen of 15 subjects (87%) showed a protective effect of lodoxamide administered 15 min prior to antigen challenge. Six of the 13 subjects who were protected initially remained protected 4 hr after lodoxamide treatment and one of these six subjects was also protected at 6 to 8 hr. One additional subject not protected at 4 hr was protected at 3 hr. Lodoxamide exhibited no bronchodilator activity and was not associated with any significant side effects. Further studies are warranted to compare the effectiveness of lodoxamide with that of cromolyn sodium in protection against antigen-induced bronchospasm and to evaluate the relative efficacy and safety of lodoxamide in long-term clinical trials.

Topics: Adolescent; Adult; Amino Acids; Antigens; Asthma; Bronchial Spasm; Dose-Response Relationship, Immunologic; Female; Forced Expiratory Volume; Humans; Male; Maximal Midexpiratory Flow Rate; Middle Aged; Nitriles; Oxamic Acid; Placebos; Respiratory Function Tests; Tromethamine

Lodoxamide tromethamine (U-42,585E) is a new drug intended for prophylaxis of mast cell-mediated allergic disease. It is a water-soluble, cromolyn-like agent with demonstrated activity in rat peritoneal mast cell assay, rat percutaneous anaphylaxis (rat PCA) and sensitized rhesus monkey airway system. Ten allergen-sensitive asthmatics were pretreated with lodoxamide (0.01, 0.1, or 1.0 mg) or placebo, then challenged with serial dilutions of allergen extract. Analysis of allergen dose-response curve parameters shows that pretreatment with lodoxamide offers significant protection against experimental allergen-induced bronchoconstriction. At 0.01 mg, lodoxamide was effective in over half the subjects tested. Administration of lodoxamide by inhalation at doses of 0.1 and 1.0 mg uniformly allowed subjects to tolerate significantly larger doses of inhaled allergen. Side effects observed at these doses were minimal.

Topics: Adolescent; Adult; Amino Acids; Analysis of Variance; Asthma; Bronchial Provocation Tests; Forced Expiratory Volume; Humans; Male; Nitriles; Oxamic Acid; Placebos; Time Factors; Tromethamine

A most active biologue of disodium cromoglycate (DSCG) available, lodoxamide tromethamine (LT), has been studied and characterized pharmacologically, in animal and human models of asthma. It has self-tachyphylaxis, but has oral activity (lodoxamide ethyl) in rats, primates, and man. In rats (LT) was 2,500 X more active than DSCG (ID50 = 0.001 mg/kg), in primates the drug was also active by several routes (inhalation 1 microgram/kg, IV 0.001 mg/kg, and oral 10 mg/kg). In isolated rat peritoneal mast cells, the compound displayed a biphasic dose response inhibition to histamine release initiated by (48/80, anti-IgE, and the calcium ionophore A23,187) with IC50 values of 0.1-50 microM. The consistent finding relating to its mode of action was its ability to inhibit 45calcium flux into the mast cell in response to antigen or A23,187. Clinical evaluations of lodoxamide tromethamine showed that at aerosol doses of 1.0 mg or less, it demonstrated significant inhibitory activity against antigen or exercise induced bronchospasm. However, in pilot evaluation studies in clinical asthma settings, the compound could not be shown to spare bronchodilator usage, relative to placebo, or be shown to be more effective than placebo treated patients based on other clinical endpoints. The reason for rat and primate models not being predictive for human long-term clinical asthma in the characterization of anti-release compounds is not known.

Topics: Amino Acids; Animals; Asthma; Calcium; Cromolyn Sodium; Disease Models, Animal; Drug Evaluation; Histamine H1 Antagonists; Humans; Macaca mulatta; Mast Cells; Nitriles; Oxamic Acid; Rats; Tromethamine