The Pharmacokinetics, Safety and Tolerability of Aclidinium Bromide 400 μg Administered by Inhalation as Single and Multiple (Twice Daily) Doses in Healthy Chinese Participants
Weimin Li,1 Sami Z Daoud,2 Roopa Trivedi,3 Pradeep B Lukka,4 Eulalia Jimenez,5 Eduard Molins,5 Catherine Stewart,6 Pranob Bharali,3,7 Esther Garcia-Gil8 1Clinical Trial Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Respiratory & Immuno...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2023-11-01
|
| Series: | International Journal of COPD |
| Subjects: | |
| Online Access: | https://www.dovepress.com/the-pharmacokinetics-safety-and-tolerability-of-aclidinium-bromide-400-peer-reviewed-fulltext-article-COPD |
| _version_ | 1797449026867560448 |
|---|---|
| author | Li W Daoud SZ Trivedi R Lukka PB Jimenez E Molins E Stewart C Bharali P Garcia-Gil E |
| author_facet | Li W Daoud SZ Trivedi R Lukka PB Jimenez E Molins E Stewart C Bharali P Garcia-Gil E |
| author_sort | Li W |
| collection | DOAJ |
| description | Weimin Li,1 Sami Z Daoud,2 Roopa Trivedi,3 Pradeep B Lukka,4 Eulalia Jimenez,5 Eduard Molins,5 Catherine Stewart,6 Pranob Bharali,3,7 Esther Garcia-Gil8 1Clinical Trial Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA; 3Late Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Durham, NC, USA; 4Clinical & Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Gaithersburg, MD, USA; 5Clinical & Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Barcelona, Spain; 6Statistics, Phastar, Chiswick, London, UK; 7BioPharmaceuticals R&D Late-Stage Development, AstraZeneca India Pvt Ltd., Bangalore, Karnataka, India; 8Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Barcelona, SpainCorrespondence: Sami Z Daoud, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, One MedImmune Way, Gaithersburg, MD, 20878, USA, Tel +1 302-598-8614, Email Sami.Daoud@astrazeneca.comPurpose: To date, aclidinium pharmacokinetic (PK) studies have focused on Caucasian populations, and no data are available for Chinese populations. We aimed to characterize the PK and safety profile of aclidinium and its metabolites (LAS34823 and LAS34850) following single and multiple (twice-daily; BID) dosing in healthy Chinese participants, and to compare PK data between Chinese and Caucasian populations.Materials and methods: In this Phase I, open-label study (NCT03276052), healthy participants from a single site in China received aclidinium bromide 400 μg via a dry powder inhaler. The Day 1 single dose was followed by a washout period of 96 hours. On Days 5 through 8, participants received BID doses.Results: Twenty healthy Chinese participants, aged 18– 45 years, were enrolled. Aclidinium absorption was rapid (median time to maximum concentration [tmax] 0.08 hours post-dose following single/multiple doses). LAS34823 had a similar median tmax of 0.08 hours, whereas LAS34850 tmax occurred later (median 2.50– 3.00 hours). Aclidinium, LAS34823, and LAS34850 concentrations declined in a bi-phasic manner; geometric mean half-life was 13.5 hours (single dosing) and 21.4 hours (multiple dosing), while steady state was generally achieved after 5 days’ continuous dosing. Area under the concentration–time curve during a dosage interval (AUCτ) metabolite to parent ratios for LAS34823 were 2.6 (Day 1) and 2.9 (Day 9), while LAS34850 had ratios of 136.0 and 94.8, respectively. Aclidinium accumulation occurred after 5 days of BID dosing (LS mean accumulation ratio for AUCτ Day 9/Day 1: 214.1% [90% CI, 176.5, 259.6]); LAS34823 accumulation was similar, while LAS34850 accumulation was lower. Between-participant exposure variability was moderate to high for aclidinium and LAS34823, and low for LAS34850.Conclusion: Single and multiple doses of aclidinium were well tolerated in healthy Chinese participants. The safety profile of and exposure to aclidinium was consistent with previous studies conducted in Caucasian populations.Keywords: aclidinium bromide, bronchodilator, China, chronic obstructive pulmonary disease, pharmacokinetics, safety |
| first_indexed | 2024-03-09T14:19:53Z |
| format | Article |
| id | doaj.art-a51ba7c6b7f74451b7e61ba5203fbd12 |
| institution | Directory Open Access Journal |
| issn | 1178-2005 |
| language | English |
| last_indexed | 2024-03-09T14:19:53Z |
| publishDate | 2023-11-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of COPD |
| spelling | doaj.art-a51ba7c6b7f74451b7e61ba5203fbd122023-11-28T17:15:53ZengDove Medical PressInternational Journal of COPD1178-20052023-11-01Volume 182725273588511The Pharmacokinetics, Safety and Tolerability of Aclidinium Bromide 400 μg Administered by Inhalation as Single and Multiple (Twice Daily) Doses in Healthy Chinese ParticipantsLi WDaoud SZTrivedi RLukka PBJimenez EMolins EStewart CBharali PGarcia-Gil EWeimin Li,1 Sami Z Daoud,2 Roopa Trivedi,3 Pradeep B Lukka,4 Eulalia Jimenez,5 Eduard Molins,5 Catherine Stewart,6 Pranob Bharali,3,7 Esther Garcia-Gil8 1Clinical Trial Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA; 3Late Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Durham, NC, USA; 4Clinical & Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Gaithersburg, MD, USA; 5Clinical & Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Barcelona, Spain; 6Statistics, Phastar, Chiswick, London, UK; 7BioPharmaceuticals R&D Late-Stage Development, AstraZeneca India Pvt Ltd., Bangalore, Karnataka, India; 8Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Barcelona, SpainCorrespondence: Sami Z Daoud, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, One MedImmune Way, Gaithersburg, MD, 20878, USA, Tel +1 302-598-8614, Email Sami.Daoud@astrazeneca.comPurpose: To date, aclidinium pharmacokinetic (PK) studies have focused on Caucasian populations, and no data are available for Chinese populations. We aimed to characterize the PK and safety profile of aclidinium and its metabolites (LAS34823 and LAS34850) following single and multiple (twice-daily; BID) dosing in healthy Chinese participants, and to compare PK data between Chinese and Caucasian populations.Materials and methods: In this Phase I, open-label study (NCT03276052), healthy participants from a single site in China received aclidinium bromide 400 μg via a dry powder inhaler. The Day 1 single dose was followed by a washout period of 96 hours. On Days 5 through 8, participants received BID doses.Results: Twenty healthy Chinese participants, aged 18– 45 years, were enrolled. Aclidinium absorption was rapid (median time to maximum concentration [tmax] 0.08 hours post-dose following single/multiple doses). LAS34823 had a similar median tmax of 0.08 hours, whereas LAS34850 tmax occurred later (median 2.50– 3.00 hours). Aclidinium, LAS34823, and LAS34850 concentrations declined in a bi-phasic manner; geometric mean half-life was 13.5 hours (single dosing) and 21.4 hours (multiple dosing), while steady state was generally achieved after 5 days’ continuous dosing. Area under the concentration–time curve during a dosage interval (AUCτ) metabolite to parent ratios for LAS34823 were 2.6 (Day 1) and 2.9 (Day 9), while LAS34850 had ratios of 136.0 and 94.8, respectively. Aclidinium accumulation occurred after 5 days of BID dosing (LS mean accumulation ratio for AUCτ Day 9/Day 1: 214.1% [90% CI, 176.5, 259.6]); LAS34823 accumulation was similar, while LAS34850 accumulation was lower. Between-participant exposure variability was moderate to high for aclidinium and LAS34823, and low for LAS34850.Conclusion: Single and multiple doses of aclidinium were well tolerated in healthy Chinese participants. The safety profile of and exposure to aclidinium was consistent with previous studies conducted in Caucasian populations.Keywords: aclidinium bromide, bronchodilator, China, chronic obstructive pulmonary disease, pharmacokinetics, safetyhttps://www.dovepress.com/the-pharmacokinetics-safety-and-tolerability-of-aclidinium-bromide-400-peer-reviewed-fulltext-article-COPDaclidinium bromidebronchodilatorchinachronic obstructive pulmonary diseasepharmacokineticssafety. |
| spellingShingle | Li W Daoud SZ Trivedi R Lukka PB Jimenez E Molins E Stewart C Bharali P Garcia-Gil E The Pharmacokinetics, Safety and Tolerability of Aclidinium Bromide 400 μg Administered by Inhalation as Single and Multiple (Twice Daily) Doses in Healthy Chinese Participants International Journal of COPD aclidinium bromide bronchodilator china chronic obstructive pulmonary disease pharmacokinetics safety. |
| title | The Pharmacokinetics, Safety and Tolerability of Aclidinium Bromide 400 μg Administered by Inhalation as Single and Multiple (Twice Daily) Doses in Healthy Chinese Participants |
| title_full | The Pharmacokinetics, Safety and Tolerability of Aclidinium Bromide 400 μg Administered by Inhalation as Single and Multiple (Twice Daily) Doses in Healthy Chinese Participants |
| title_fullStr | The Pharmacokinetics, Safety and Tolerability of Aclidinium Bromide 400 μg Administered by Inhalation as Single and Multiple (Twice Daily) Doses in Healthy Chinese Participants |
| title_full_unstemmed | The Pharmacokinetics, Safety and Tolerability of Aclidinium Bromide 400 μg Administered by Inhalation as Single and Multiple (Twice Daily) Doses in Healthy Chinese Participants |
| title_short | The Pharmacokinetics, Safety and Tolerability of Aclidinium Bromide 400 μg Administered by Inhalation as Single and Multiple (Twice Daily) Doses in Healthy Chinese Participants |
| title_sort | pharmacokinetics safety and tolerability of aclidinium bromide 400 nbsp mu g administered by inhalation as single and multiple twice daily doses in healthy chinese participants |
| topic | aclidinium bromide bronchodilator china chronic obstructive pulmonary disease pharmacokinetics safety. |
| url | https://www.dovepress.com/the-pharmacokinetics-safety-and-tolerability-of-aclidinium-bromide-400-peer-reviewed-fulltext-article-COPD |
| work_keys_str_mv | AT liw thepharmacokineticssafetyandtolerabilityofaclidiniumbromide400nbspmugadministeredbyinhalationassingleandmultipletwicedailydosesinhealthychineseparticipants AT daoudsz thepharmacokineticssafetyandtolerabilityofaclidiniumbromide400nbspmugadministeredbyinhalationassingleandmultipletwicedailydosesinhealthychineseparticipants AT trivedir thepharmacokineticssafetyandtolerabilityofaclidiniumbromide400nbspmugadministeredbyinhalationassingleandmultipletwicedailydosesinhealthychineseparticipants AT lukkapb thepharmacokineticssafetyandtolerabilityofaclidiniumbromide400nbspmugadministeredbyinhalationassingleandmultipletwicedailydosesinhealthychineseparticipants AT jimeneze thepharmacokineticssafetyandtolerabilityofaclidiniumbromide400nbspmugadministeredbyinhalationassingleandmultipletwicedailydosesinhealthychineseparticipants AT molinse thepharmacokineticssafetyandtolerabilityofaclidiniumbromide400nbspmugadministeredbyinhalationassingleandmultipletwicedailydosesinhealthychineseparticipants AT stewartc thepharmacokineticssafetyandtolerabilityofaclidiniumbromide400nbspmugadministeredbyinhalationassingleandmultipletwicedailydosesinhealthychineseparticipants AT bharalip thepharmacokineticssafetyandtolerabilityofaclidiniumbromide400nbspmugadministeredbyinhalationassingleandmultipletwicedailydosesinhealthychineseparticipants AT garciagile thepharmacokineticssafetyandtolerabilityofaclidiniumbromide400nbspmugadministeredbyinhalationassingleandmultipletwicedailydosesinhealthychineseparticipants AT liw pharmacokineticssafetyandtolerabilityofaclidiniumbromide400nbspmugadministeredbyinhalationassingleandmultipletwicedailydosesinhealthychineseparticipants AT daoudsz pharmacokineticssafetyandtolerabilityofaclidiniumbromide400nbspmugadministeredbyinhalationassingleandmultipletwicedailydosesinhealthychineseparticipants AT trivedir pharmacokineticssafetyandtolerabilityofaclidiniumbromide400nbspmugadministeredbyinhalationassingleandmultipletwicedailydosesinhealthychineseparticipants AT lukkapb pharmacokineticssafetyandtolerabilityofaclidiniumbromide400nbspmugadministeredbyinhalationassingleandmultipletwicedailydosesinhealthychineseparticipants AT jimeneze pharmacokineticssafetyandtolerabilityofaclidiniumbromide400nbspmugadministeredbyinhalationassingleandmultipletwicedailydosesinhealthychineseparticipants AT molinse pharmacokineticssafetyandtolerabilityofaclidiniumbromide400nbspmugadministeredbyinhalationassingleandmultipletwicedailydosesinhealthychineseparticipants AT stewartc pharmacokineticssafetyandtolerabilityofaclidiniumbromide400nbspmugadministeredbyinhalationassingleandmultipletwicedailydosesinhealthychineseparticipants AT bharalip pharmacokineticssafetyandtolerabilityofaclidiniumbromide400nbspmugadministeredbyinhalationassingleandmultipletwicedailydosesinhealthychineseparticipants AT garciagile pharmacokineticssafetyandtolerabilityofaclidiniumbromide400nbspmugadministeredbyinhalationassingleandmultipletwicedailydosesinhealthychineseparticipants |