DETERMINATION OF THE RELATIVE BIOAVAILABILITY OF NEDOCROMIL SODIUM TOTHE LUNG FOLLOWING INHALATION USING URINARY-EXCRETION

Objective: To determine the relative lung deposition of nedocromil sod ium following inhalation by comparing the amounts of nedocromil sodium excreted in the urine after oral and inhaled dosing. Methods: Ten hea lthy volunteers swallowed 8 mg of nedocromil and inhaled 4 x 2-mg dose s on separate days. Urine was collected at 0.0, 0.5, 1.0, 2.0, 5.0, 24 h and 36 h after dosing. Urinary excretion of nedocromil was determin ed by high-performance liquid chromatography. Results: A significantly greater amount of nedocromil was excreted following inhalation than a fter oral dosing. The mean with (SD) amount excreted at 0.5, 1.0 h and 24 h following inhalation of 4 x 2-mg doses was 41.0 (19.5), 93.0 (39 .1) and 319.9 (138.1) mu g. Corresponding values after oral administra tion of 8 mg of nedocromil were 2.1 (2.2), 6.3 (4.7) mu g and 74.4 (58 .8) mu g, respectively. Conclusion: Nedocromil excreted in the urine a t 0.5 h and 1.0 h after dosing is representative of the amount of drug delivered to the lungs. This method could be used to compare the rela tive bioavailability to the lungs following inhalation, and hence the performance of different inhaled products and inhalation techniques. T he amount of nedocromil excreted in 24 h post-dose is representative o f the emitted dose which was delivered to the body.