Tolerability and pharmacokinetic evaluation of inhaled dry powder hydroxychloroquine in healthy volunteers
Y A De Reus, P Hagedoorn, M G G Sturkenboom, F Grasmeijer, M S Bolhuis, I Sibum, H A M Kerstjens, H W Frijlink, O W Akkerman
PLOS ONE, doi:10.1371/journal.pone.0272034
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 FEV 1 post inhalation. The serum HCQ concentration remained below 10 μg/L in all samples.
Supporting information
S1 Checklist. CONSORT checklist. (DOC)
Author Contributions
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doi:10.1056/NEJMoa2001017{ 'indexed': {'date-parts': [[2023, 7, 5]], 'date-time': '2023-07-05T19:28:41Z', 'timestamp': 1688585321694},
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'abstract': '<jats:sec id="sec001">\n'
'<jats:title>Rationale</jats:title>\n'
'<jats:p>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.</jats:p>\n'
'</jats:sec>\n'
'<jats:sec id="sec002">\n'
'<jats:title>Objectives</jats:title>\n'
'<jats:p>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.</jats:p>\n'
'</jats:sec>\n'
'<jats:sec id="sec003">\n'
'<jats:title>Methods</jats:title>\n'
'<jats:p>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.</jats:p>\n'
'</jats:sec>\n'
'<jats:sec id="sec004">\n'
'<jats:title>Results and discussion</jats:title>\n'
'<jats:p>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 FEV<jats:sub>1</jats:sub> post inhalation. The '
'serum HCQ concentration remained below 10 μg/L in all samples.</jats:p>\n'
'</jats:sec>\n'
'<jats:sec id="sec005">\n'
'<jats:title>Conclusion</jats:title>\n'
'<jats:p>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.</jats:p>\n'
'</jats:sec>',
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