Abstract
Purpose: The dose combination of ipratropium bromide (Ip) 42 mcg and albuterol (Alb) 200 mcg, propelled by CFC, is currently marketed in a single canister dosage form. A soft-spray, aqueous solution-based delivery system of this combination was developed. This pharmacokinetic study compared the efficiency of a soft-spray delivery of the combination to the lung compared to CFC delivery.
Methods: A steady state pharmacokinetic substudy comprised of 278 patients was conducted from two trials differing only by doses evaluating Ip and Alb delivered via the soft-spray inhaler or CFC-MDI in 2,578 patients. Ip alone delivered via the soft-spray inhaler and placebos delivered via either delivery system were used as controls. LC/MS/MS assays for analytes were developed for plasma and urine biofluids.
Results: Comparing AUC, Cmax, and Cmin showed that systemic exposure to Alb and Ip delivered via the soft-spray inhaler were proportional to the doses delivered. Comparability was obtained when comparing the soft-spray inhaler-delivered Ip at half the dose of the CFC-MDI. Since Ip is not significantly absorbed from the gastrointestinal tract, the systemic exposure observed is a relevant marker for lung deposition. Ip alone gave equivalent exposure as the combination demonstrating a lack of interaction.
Conclusions: These systemic exposure analyses can be regarded as a marker of lung deposition and therefore demonstrate that the soft-spray inhaler delivers drug more efficiently to the lung than CFC-MDI.
- © 2011 ERS