title: Effect of Inhaled Interferon Beta-1a on Carbon Monoxide Transfer Factor in Healthy Volunteers.
abstract: Interferon beta-1a (IFNβ-1a) 30 μg weekly by intramuscular (IM) injection is used to treat relapsing forms of multiple sclerosis. We assessed if it can be given safely by inhalation. Twenty-one healthy volunteers inhaled IFNβ-1a 300 μg, formulated for deep delivery to the lungs, in a randomized, parallel-group, repeat-dose trial. Comparators were room air and placebo. The primary outcome measure was carbon monoxide transfer factor corrected for hemoglobin (TLCOc), which measures the CO transfer from inspired gas to pulmonary capillary blood. After 3 and 4 once-weekly doses, IFNβ-1a significantly reduced TLCOc compared with room air: after the third dose, mean standard deviation (SD) change in percent predicted TLCOc was-10.9 (2.8), and after the fourth dose was-12.1 (2.7). After 2, 3, and 4 doses, IFNβ-1a significantly reduced TLCOc compared with placebo: after the second dose, mean (SD) change in percent predicted TLCOc was-8.8 (5.5), after the third dose was-10.9 (2.8), and after the fourth dose was-12.1 (2.7). Circulating IFNβ-1a concentrations were about one-third those of the intramuscular dose regimen. Tolerability of IFNβ-1a and the comparators was equally good. In conclusion, IFNβ-1a reduced TLCOc, whereas placebo and room air did not. A dose of IFNβ-1a 300 μg by inhalation may not be safe for general use.
authors.affiliation: Hammersmith Medicines Research , London, United Kingdom .
authors.forename: Virginia
authors.initials: V
authors.lastname: Norris
authors.affiliation: Hammersmith Medicines Research , London, United Kingdom .
authors.forename: Steve
authors.initials: S
authors.lastname: Warrington
authors.affiliation: Hammersmith Medicines Research , London, United Kingdom .
authors.forename: Malcolm
authors.initials: M
authors.lastname: Boyce
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D002248:Carbon Monoxide / Q000378:metabolism*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D000068556:Interferon beta-1a / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008297:Male; D012129:Respiratory Function Tests; D055815:Young Adult
chemical_list: D002248:Carbon Monoxide; D000068556:Interferon beta-1a