Tolerability and pharmacokinetic evaluation of inhaled dry powder hydroxychloroquine in healthy volunteers.

Rationale: Inhaled antimicrobials enable high local concentrations where needed and, compared to orally administration, greatly reduce the potential for systemic side effects. In SARS-CoV-2 infections, hydroxychloroquine sulphate (HCQ) administered as dry powder via inhalation could be safer than oral HCQ allowing higher and therefore more effective pulmonary concentrations without dose limiting toxic effects.
Objectives: To assess the local tolerability, safety and pharmacokinetic parameters of HCQ inhalations in single ascending doses of 5, 10 and 20 mg using the Cyclops dry powder inhaler.
Methods: Twelve healthy volunteers were included in the study. Local tolerability and safety were assessed by pulmonary function tests, electrocardiogram and recording adverse events. To estimate systemic exposure, serum samples were collected before and 0.5, 2 and 3.5 h after inhalation.
Results and Discussion: Dry powder HCQ inhalations were well tolerated by the participants, except for transient bitter taste in all participants and minor coughing irritation. There was no significant change in QTc-interval or drop in FEV1 post inhalation. The serum HCQ concentration remained below 10 μg/L in all samples.
Conclusion: Single doses of inhaled dry powder HCQ up to 20 mg are safe and well tolerated. Our data support that further studies with inhaled HCQ dry powder to evaluate pulmonary pharmacokinetics and efficacy are warranted.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: The employer Prof. Dr. H.W. Frijlink and P. Hagedoorn has a license agreement with PureIMS on the Cyclops patent (WO2015/187025) and receives royalty payments over the sales of the Novolizer®, Genuair®/Pressair® and Cyclops dry powder inhalers. In addition, Prof. Dr. H.W. Frijlink and Paul Hagedoorn have a patent WO2015NL50413 20150605 licensed. Floris Grasmeijer is employed by PureIMS, the manufacturer of the Cyclops inhaler. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials. The other authors have no conflicts of interest to declare.’