Improved bioavailability of cromolyn sodium using inhaled PA101 delivered via eFlow® nebulizer

In 1960s, cromolyn sodium (CS) has been introduced as the first non-steroidal anti-inflammatory drug for the treatment of allergic and mast-cell driven diseases. Its applicability has been limited due to a poor bioavailability. Here we present pharmacokinetic data of a novel high concentration formulation of CS (PA101) delivered via a high-efficiency nebulizer (eFlow®) in healthy volunteers (HVs), allergic asthmatics and patients with indolent systemic mastocytosis (ISM). In HVs, PA101 40 mg and 80 mg (30 L) and PA101 40 mg (40 L), Intal(TM) (via LC® Plus) 20 mg and Nalcrom® (oral suspension) 200 mg showed maximum measured plasma concentration (C(max)) of 156, 236, 88.6, 17.8 and 5.23 ng/mL, respectively, with respective areas under the plasma time-concentration curve (AUC) of 338, 526, 212, 40.6 and 33.3 h·ng/mL. Systemic exposure (AUC) to CS with PA101 40 mg was approximately 8-fold and 11-fold higher compared to Intal(TM) and Nalcrom® in HVs, respectively. PA101 via eFlow® yielded comparable PK profiles in HVs and patients. Systemic bioavailability of PA101 was approximately 25% compared to approximately 1% for Nalcrom® and approximately 10% for Intal(TM), respectively. These data warrant further research on the therapeutic potential of PA101 (via eFlow®) in allergic and mast-cell driven diseases.