A new dry powder inhaler, the Ultrahaler, has been developed to deliver nedocromil sodium for the prophylaxis of asthma. This study was performed to compare the lung deposition of nedocromil sodium inhaled from the Ultrahaler at two different inhaled flow rates with that from a pressurised metered dose inhaler (MDI). A scintigraphic study was conducted in 12 healthy volunteers. On each study day, volunteers received a single 4.2 mg dose of nedocromil sodium from the Ultrahaler, using either an optimal (fast) inhaled flow rate or a suboptimal (slow) inhaled flow rate, or two doses of 2 mg nedocromil sodium from an MDI using an optimal (slow) inhaled flow rate. Used optimally, the Ultrahaler deposited significantly more (p < 0.05) of the metered dose in the lungs than either the Ultrahaler used suboptimally or the MDI used optimally [mean (SD) lung deposition values of 13.3 (4.8)%, 9.8 (3.5)%, and 7.5 (2.9)%, respectively]. Oropharyngeal deposition averaged over 80% of the dose for all three treatment regimens. This scintigraphic study demonstrated in vivo proof of concept for the Ultrahaler dry powder inhaler, and provided quantitative data on the relationship in lung deposition between the Ultrahaler and MDI which differed from that predicted by the in vitro fine particle fraction.
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.
The bioavailability of a single dose of d-pseudoephedrine sulfate administered to male volunteers in repeat action tablet form (60 mg d-pseudoephedrine sulfate in the coat and 60 mg d-pseudoephedrine sulfate in the core) was compared with the bioavailability of an equivalent quantity of the drug given as two 60 mg conventional tablets, one given at 0 hour and the second 6 hours later. There was no significant difference (P less than 0.10) between the conventional tablets and the repeat action tablet formulation in area under the plasma concentration-time curve and the maximum plasma concentration of d-pseudoephedrine. Based on the data, we conclude that the repeat action tablet formulation and the conventional tablet are bioequivalent.
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