Bioavailability and Metabolism of Mometasone Furoate following Administration by Metered-Dose and Dry-Powder Inhalers in Healthy Human Volunteers

• Published in: Journal of clinical pharmacology 2000-11, Vol.40 (11), p.1227-1236
• Main Authors: Affrime, Melton B., Cuss, Francis, Padhi, Desmond, Wirth, Mark, Pai, Sudhakar, Clement, Robert P., Lim, Josephine, Kantesaria, Bhavna, Alton, Kevin, Cayen, Mitchell N.
• Format: Article
• Language: English
• Subjects: Absorption; Anti-Inflammatory Agents - pharmacokinetics; Biological and medical sciences; Biological Availability; Cross-Over Studies; Female; Humans; Male; Medical sciences; Mometasone Furoate; Nebulizers and Vaporizers; Pharmacology. Drug treatments; Powders; Pregnadienediols - administration & dosage; Pregnadienediols - pharmacokinetics; Respiratory system
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1177/009127000004001107

These studies were conducted to assess the systemic bioavailability of mometasone furoate (MF) administered by both the dry‐powder inhaler (DPI) and the metered‐dose inhaler with an alternate propellant (MDI‐AP). The pharmacokinetics of single doses (400 μg) of MF administered by intravenous (IV) and inhalation routes was assessed in a randomized, three‐way crossover study involving 24 healthy volunteers. In a separate study, 6 healthy subjects were administered a single dose of tritiated (3H‐) MF by DPI, and the radioactivity in blood, urine, feces, and expired air was determined. Following IV administration, MF was detected in all subjects for at least 8 hours postdose. The half‐life (t1/2) following IV administration was 4.5 hours. In contrast, following DPI administration, plasma MF concentrations were below the limit of quantification (LOQ, 50 pg/mL) for many subjects (10 of 24), and the systemic bioavailability by this route was estimated to be less than 1%. Only two plasma samples following MDI‐AP administration had plasma concentrations of MF above the LOQ, indicating no detectable systemic bioavailability in 92% of the subjects. A separate study with 6 healthy male subjects administered a single dose of3H‐MF (200 μCi) by DPI revealed that much of the dose (∼ 41%) was excreted unchanged in the feces (0–72 hours), while that which was absorbed was extensively metabolized. These results indicate that inhaled MF has negligible systemic bioavailability and is extensively metabolized and should therefore be well tolerated in the chronic treatment of asthma.