RADIO LABELING OF DRUGS IN A METERED-DOSE INHALER (MDI) AND LUNG DEPOSITION IN HUMAN-SUBJECTS

The lung deposition (amount and distribution) of drugs from MDIs canno t be quantified using routine pharmacokinetic methods. A growing numbe r of drugs from inhalers has been investigated in recent years using a radiolabel to overcome this difficulty. Fenoterol (Berotec(R)) and Fl unisolide (Inhacort(R)) both from Boehringer Ingelheim KG are two drug s primarily used by inhalation in the treatment of asthma. These compo unds were labelled with Technetium-99m (Tc) in the MDI. The Tc-99m lab el as observed with a gamma camera was shown to follow the same distri bution pattern as the drug particles. Cascade impaction with eight sta ges resulted in the following distribution 63, 8, 5, 3, 6, 5, 8, and 2 % from Stage 1 to Stage 8. A clinical study with 12 healthy volunteer s compared the deposition pattern derived from MDI alone and MDI with spacer. Regions Of Interest (ROIs) were the oropharyngal cavity, esoph agus, stomach, and lung (central and peripheral zones). With MDI alone , 73 % of the drug was found in upper ROIs, whereas the addition of a spacer reduced deposition of the drug in the large airways to 3 %. Thi s technique may also be a valuable tool in comparing different formula tions; however the stability of Tc-99m binding to the drug particles s hould be evaluated before utilizing this technique.