General: Nedocromil sodium has been shown to inhibit the in vitro activation of, and mediator release from, a variety of inflammatory cell types associated with asthma, including eosinophils, neutrophils, macrophages, mast cells, monocytes, and platelets. In vitro studies on cells obtained by bronchoalveolar lavage from antigen-sensitized macaque monkeys show that nedocromil sodium inhibits the release of mediators including histamine, leukotriene C₄, and prostaglandin D₂. Similar studies with human bronchoalveolar cells showed inhibition of histamine release from mast cells and beta-glucuronidase release from macrophages.

Nedocromil sodium has been tested in experimental models of asthma using allergic animals and shown to inhibit the development of early and late bronchoconstriction responses to inhaled antigen. The development of airway hyper-responsiveness to nonspecific bronchoconstrictors was also inhibited. Nedocromil sodium reduced antigen-induced increases in airway microvasculature leakage when administered intravenously in a model system.

In humans, nedocromil sodium has been shown to inhibit acutely the bronchoconstrictor response to several kinds of challenge. Pretreatment with single doses of nedocromil sodium inhibited the bronchoconstriction caused by sulfur dioxide, inhaled neurokinin A, various antigens, exercise, cold air, fog, and adenosine monophosphate.

Nedocromil sodium has no bronchodilator, antihistamine, or corticosteroid activity.

Nedocromil sodium, when delivered by inhalation at the recommended dose, has no known systemic activity.

Pharmacokinetics and Bioavailability: Systemic bioavailability of nedocromil sodium administered as an inhaled aerosol is low. In a single dose study involving 20 healthy adult subjects who were administered a 3.5 mg dose of nedocromil sodium (2 actuations of 1.75 mg each), the mean AUC was 5.0 ng·hr/mL and the mean Cmax was 1.6 ng/mL attained about 28 minutes after dosing. The mean half-life was 3.3 hours. Urinary excretion over 12 hours averaged 3.4% of the administered dose, of which approximately 75% was excreted in the first six hours of dosing.

In a multiple dose study, six healthy adult volunteers (3 males and 3 females) received a 3.5 mg single dose followed by 3.5 mg four times a day for seven consecutive days. Accumulation of the drug was not observed. Following single and multiple dose inhalations, urinary excretion of nedocromil accounted for 5.6% and 12% of the drug administered, respectively. After intravenous administration to healthy adults, urinary excretion of nedocromil was approximately 70%. The absolute bioavailability of nedocromil was thus 8% (5.6/70) for single and 17% (12/70) for multiple inhaled doses.

Similarly, in a multiple dose study of 12 asthmatic adult patients, each given a 3.5 mg single dose followed by 3.5 mg four times a day for one month, both single dose and multiple dose inhalations gave a mean high plasma concentration of 2.8 ng/mL between 5 and 90 minutes, mean AUC of 5.6 ng-hr/mL, and a mean terminal half-life of 1.5 hours. The mean 24-hour urinary excretion after either single or multiple dose administration represented approximately 5% of the administered dose.

Studies involving very high oral doses of nedocromil (600 mg single dose, and subsequently 200 mg three times a day for seven days) showed an absolute bioavailability of less than 2%. In a radiolabeled (¹⁴C) nedocromil intravenous study involving two healthy adult males, urinary excretion accounted for 64% of the dose, fecal excretion for 36%.

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