Bioavailability and metabolism of mometasone furoate following administration by metered-dose and dry-powder inhalers in healthy human volunteers

These studies were conducted to assess the systemic bioavailability of mome tasone furoate (MF) administered by both the dry-powder inhaler (DPI) and t he metered-dose inhaler with an alternate propellant (MDI-AP),. The pharmac okinetics of single doses (400 mu g) of MF administered by intravenous (IV) and inhalation routes was assessed in a randomized, three-way crossover st udy involving 24 healthy volunteers. In a separate study, 6 healthy subject s were administered a single dose of tritiated (H-3-) MF by DPI, and the ra dioactivity in blood, urine, feces, and expired air was determined. Followi ng IV administration, MF was detected in all subjects for at least 8 hours postdose. The half-life (t(1/2)) following IV administration was 4.5 hours. In contrast, following DPI administration, plasma MF concentrations were b elow the limit of quantification (LOQ, 50 pg/mL) for many subjects (10 of 2 4), and the systemic bioavailability by this route was estimated to be less than 1%. Only two plasma samples following MDI-AP administration had plasm a concentrations of MF above the LOQ, indicating no detectable systemic bio availability in 92% of the subjects. A separate study with 6 healthy male s ubjects administered a single dose of H-3-MF (200 mu Ci) by DPI revealed th at much of the dose ( approximate to 41%) was excreted unchanged in the fec es (0-72 hours), while that which was absorbed was extensively metabolized. These results indicate that inhaled MF has negligible systemic bioavailabi lity and is extensively metabolized and should therefore be well tolerated in the chronic treatment of asthma. (C)2000 the American College of Clinica l Pharmacology.