Evaluating the pharmacokinetics of beclometasone dipropionate/formoterol fumarate/glycopyrronium bromide delivered via pressurised metered-dose inhaler using a low global warming potential propellant
Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved..
INTRODUCTION: Use of propellants with high global warming potential (such as HFA-134a) for pressurised metered-dose inhalers (pMDIs) is being phased down. Switching to dry-powder inhalers may not be clinically feasible for all patients; an alternative is reformulation using propellants with low global warming potential. The combination of beclometasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FF/GB) is available for asthma or chronic obstructive pulmonary disease via pMDI using HFA-134a as propellant. This is being reformulated using the low global warming potential propellant HFA-152a. This manuscript reports three studies comparing BDP/FF/GB pharmacokinetics delivered via pMDI using HFA-152a vs HFA-134a.
METHODS: The studies were four-way crossover, single-dose, randomised, double-blind, in healthy volunteers. In Studies 1 and 2, subjects inhaled four puffs of BDP/FF/GB (Study 1: 100/6/12.5 μg [medium-strength BDP]; Study 2: 200/6/12.5 μg [high-strength]), ingesting activated charcoal in two of the periods (once per propellant). In Study 3, subjects inhaled medium- and high-strength BDP/FF/GB using a spacer. All three studies compared HFA-152a vs HFA-134a in terms of lung availability and total systemic exposure of beclometasone-17-monopropionate (B17MP; active metabolite of BDP), BDP, formoterol and GB. Bioequivalence was concluded if the 90 % confidence intervals (CIs) of the ratios between formulations of the geometric mean maximum plasma concentration (Cmax) and area under the plasma concentration-time curve between time zero and the last quantifiable timepoint (AUC0-t) for the analytes were between 80 and 125 %.
RESULTS: In Studies 1 and 2, systemic exposure bioequivalence (i.e., comparisons without charcoal block) was demonstrated, except for GB Cmax in Study 2 (upper 90 % CI 125.11 %). For lung availability (i.e., comparisons with charcoal block), B17MP and formoterol demonstrated bioequivalence in both studies, as did BDP in Study 2; in Study 1, BDP upper CIs were 126.96 % for Cmax and 127.34 % for AUC0-t). In Study 1, GB AUC0-t lower CI was 74.54 %; in Study 2 upper limits were 135.64 % for Cmax and 129.12 % for AUC0-t. In Study 3, the bioequivalence criteria were met for BDP, B17MP and formoterol with both BDP/FF/GB strengths, and were met for GB AUC0-t, although not for Cmax. Both formulations were similarly well tolerated in all three studies.
CONCLUSIONS: Overall, while formal bioequivalence cannot be concluded for all analytes, these data suggest therapeutic equivalence of the new formulation with the existing BDP/FF/GB pMDI formulation, therefore supporting reformulation using a propellant with low global warming potential.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2024 |
---|---|
Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:85 |
---|---|
Enthalten in: |
Pulmonary pharmacology & therapeutics - 85(2024) vom: 23. Apr., Seite 102299 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Rony, François [VerfasserIn] |
---|
Links: |
---|
Themen: |
Adrenergic beta-2 receptor agonists |
---|
Anmerkungen: |
Date Revised 30.04.2024 published: Print-Electronic Citation Status Publisher |
---|
doi: |
10.1016/j.pupt.2024.102299 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM371523664 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM371523664 | ||
003 | DE-627 | ||
005 | 20240501233333.0 | ||
007 | cr uuu---uuuuu | ||
008 | 240426s2024 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1016/j.pupt.2024.102299 |2 doi | |
028 | 5 | 2 | |a pubmed24n1394.xml |
035 | |a (DE-627)NLM371523664 | ||
035 | |a (NLM)38663512 | ||
035 | |a (PII)S1094-5539(24)00015-4 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Rony, François |e verfasserin |4 aut | |
245 | 1 | 0 | |a Evaluating the pharmacokinetics of beclometasone dipropionate/formoterol fumarate/glycopyrronium bromide delivered via pressurised metered-dose inhaler using a low global warming potential propellant |
264 | 1 | |c 2024 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Revised 30.04.2024 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status Publisher | ||
520 | |a Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved. | ||
520 | |a INTRODUCTION: Use of propellants with high global warming potential (such as HFA-134a) for pressurised metered-dose inhalers (pMDIs) is being phased down. Switching to dry-powder inhalers may not be clinically feasible for all patients; an alternative is reformulation using propellants with low global warming potential. The combination of beclometasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FF/GB) is available for asthma or chronic obstructive pulmonary disease via pMDI using HFA-134a as propellant. This is being reformulated using the low global warming potential propellant HFA-152a. This manuscript reports three studies comparing BDP/FF/GB pharmacokinetics delivered via pMDI using HFA-152a vs HFA-134a | ||
520 | |a METHODS: The studies were four-way crossover, single-dose, randomised, double-blind, in healthy volunteers. In Studies 1 and 2, subjects inhaled four puffs of BDP/FF/GB (Study 1: 100/6/12.5 μg [medium-strength BDP]; Study 2: 200/6/12.5 μg [high-strength]), ingesting activated charcoal in two of the periods (once per propellant). In Study 3, subjects inhaled medium- and high-strength BDP/FF/GB using a spacer. All three studies compared HFA-152a vs HFA-134a in terms of lung availability and total systemic exposure of beclometasone-17-monopropionate (B17MP; active metabolite of BDP), BDP, formoterol and GB. Bioequivalence was concluded if the 90 % confidence intervals (CIs) of the ratios between formulations of the geometric mean maximum plasma concentration (Cmax) and area under the plasma concentration-time curve between time zero and the last quantifiable timepoint (AUC0-t) for the analytes were between 80 and 125 % | ||
520 | |a RESULTS: In Studies 1 and 2, systemic exposure bioequivalence (i.e., comparisons without charcoal block) was demonstrated, except for GB Cmax in Study 2 (upper 90 % CI 125.11 %). For lung availability (i.e., comparisons with charcoal block), B17MP and formoterol demonstrated bioequivalence in both studies, as did BDP in Study 2; in Study 1, BDP upper CIs were 126.96 % for Cmax and 127.34 % for AUC0-t). In Study 1, GB AUC0-t lower CI was 74.54 %; in Study 2 upper limits were 135.64 % for Cmax and 129.12 % for AUC0-t. In Study 3, the bioequivalence criteria were met for BDP, B17MP and formoterol with both BDP/FF/GB strengths, and were met for GB AUC0-t, although not for Cmax. Both formulations were similarly well tolerated in all three studies | ||
520 | |a CONCLUSIONS: Overall, while formal bioequivalence cannot be concluded for all analytes, these data suggest therapeutic equivalence of the new formulation with the existing BDP/FF/GB pMDI formulation, therefore supporting reformulation using a propellant with low global warming potential | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Adrenergic beta-2 receptor agonists | |
650 | 4 | |a Inhaled corticosteroids | |
650 | 4 | |a Inhaled triple therapy | |
650 | 4 | |a Lung bioavailability | |
650 | 4 | |a Muscarinic antagonists | |
650 | 4 | |a Total systemic exposure | |
700 | 1 | |a Cortellini, Mauro |e verfasserin |4 aut | |
700 | 1 | |a Guasconi, Alessandro |e verfasserin |4 aut | |
700 | 1 | |a Mathews, Kusum S |e verfasserin |4 aut | |
700 | 1 | |a Piccinno, Annalisa |e verfasserin |4 aut | |
700 | 1 | |a Poli, Gianluigi |e verfasserin |4 aut | |
700 | 1 | |a Vanhoutte, Frédéric |e verfasserin |4 aut | |
700 | 1 | |a Klein, Jelle |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Pulmonary pharmacology & therapeutics |d 1997 |g 85(2024) vom: 23. Apr., Seite 102299 |w (DE-627)NLM092899625 |x 1522-9629 |7 nnns |
773 | 1 | 8 | |g volume:85 |g year:2024 |g day:23 |g month:04 |g pages:102299 |
856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.pupt.2024.102299 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 85 |j 2024 |b 23 |c 04 |h 102299 |