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Population Pharmacodynamic Modeling and Simulation of the Respiratory Effect of Acetazolamide in Decompensated COPD Patients
BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients may develop metabolic alkalosis during weaning from mechanical ventilation. Acetazolamide is one of the treatments used to reverse metabolic alkalosis. METHODS: 619 time-respiratory (minute ventilation, tidal volume and respiratory ra...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895035/ https://www.ncbi.nlm.nih.gov/pubmed/24466018 http://dx.doi.org/10.1371/journal.pone.0086313 |
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author | Heming, Nicholas Urien, Saïk Fulda, Virginie Meziani, Ferhat Gacouin, Arnaud Clavel, Marc Planquette, Benjamin Faisy, Christophe |
author_facet | Heming, Nicholas Urien, Saïk Fulda, Virginie Meziani, Ferhat Gacouin, Arnaud Clavel, Marc Planquette, Benjamin Faisy, Christophe |
author_sort | Heming, Nicholas |
collection | PubMed |
description | BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients may develop metabolic alkalosis during weaning from mechanical ventilation. Acetazolamide is one of the treatments used to reverse metabolic alkalosis. METHODS: 619 time-respiratory (minute ventilation, tidal volume and respiratory rate) and 207 time-PaCO(2) observations were obtained from 68 invasively ventilated COPD patients. We modeled respiratory responses to acetazolamide in mechanically ventilated COPD patients and then simulated the effect of increased amounts of the drug. RESULTS: The effect of acetazolamide on minute ventilation and PaCO(2) levels was analyzed using a nonlinear mixed effect model. The effect of different ventilatory modes was assessed on the model. Only slightly increased minute ventilation without decreased PaCO(2) levels were observed in response to 250 to 500 mg of acetazolamide administered twice daily. Simulations indicated that higher acetazolamide dosage (>1000 mg daily) was required to significantly increase minute ventilation (P<.001 vs pre-acetazolamide administration). Based on our model, 1000 mg per day of acetazolamide would increase minute ventilation by >0.75 L min(−1) in 60% of the population. The model also predicts that 45% of patients would have a decrease of PaCO2>5 mmHg with doses of 1000 mg per day. CONCLUSIONS: Simulations suggest that COPD patients might benefit from the respiratory stimulant effect after the administration of higher doses of acetazolamide. |
format | Online Article Text |
id | pubmed-3895035 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38950352014-01-24 Population Pharmacodynamic Modeling and Simulation of the Respiratory Effect of Acetazolamide in Decompensated COPD Patients Heming, Nicholas Urien, Saïk Fulda, Virginie Meziani, Ferhat Gacouin, Arnaud Clavel, Marc Planquette, Benjamin Faisy, Christophe PLoS One Research Article BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients may develop metabolic alkalosis during weaning from mechanical ventilation. Acetazolamide is one of the treatments used to reverse metabolic alkalosis. METHODS: 619 time-respiratory (minute ventilation, tidal volume and respiratory rate) and 207 time-PaCO(2) observations were obtained from 68 invasively ventilated COPD patients. We modeled respiratory responses to acetazolamide in mechanically ventilated COPD patients and then simulated the effect of increased amounts of the drug. RESULTS: The effect of acetazolamide on minute ventilation and PaCO(2) levels was analyzed using a nonlinear mixed effect model. The effect of different ventilatory modes was assessed on the model. Only slightly increased minute ventilation without decreased PaCO(2) levels were observed in response to 250 to 500 mg of acetazolamide administered twice daily. Simulations indicated that higher acetazolamide dosage (>1000 mg daily) was required to significantly increase minute ventilation (P<.001 vs pre-acetazolamide administration). Based on our model, 1000 mg per day of acetazolamide would increase minute ventilation by >0.75 L min(−1) in 60% of the population. The model also predicts that 45% of patients would have a decrease of PaCO2>5 mmHg with doses of 1000 mg per day. CONCLUSIONS: Simulations suggest that COPD patients might benefit from the respiratory stimulant effect after the administration of higher doses of acetazolamide. Public Library of Science 2014-01-17 /pmc/articles/PMC3895035/ /pubmed/24466018 http://dx.doi.org/10.1371/journal.pone.0086313 Text en © 2014 Heming et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Heming, Nicholas Urien, Saïk Fulda, Virginie Meziani, Ferhat Gacouin, Arnaud Clavel, Marc Planquette, Benjamin Faisy, Christophe Population Pharmacodynamic Modeling and Simulation of the Respiratory Effect of Acetazolamide in Decompensated COPD Patients |
title | Population Pharmacodynamic Modeling and Simulation of the Respiratory Effect of Acetazolamide in Decompensated COPD Patients |
title_full | Population Pharmacodynamic Modeling and Simulation of the Respiratory Effect of Acetazolamide in Decompensated COPD Patients |
title_fullStr | Population Pharmacodynamic Modeling and Simulation of the Respiratory Effect of Acetazolamide in Decompensated COPD Patients |
title_full_unstemmed | Population Pharmacodynamic Modeling and Simulation of the Respiratory Effect of Acetazolamide in Decompensated COPD Patients |
title_short | Population Pharmacodynamic Modeling and Simulation of the Respiratory Effect of Acetazolamide in Decompensated COPD Patients |
title_sort | population pharmacodynamic modeling and simulation of the respiratory effect of acetazolamide in decompensated copd patients |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895035/ https://www.ncbi.nlm.nih.gov/pubmed/24466018 http://dx.doi.org/10.1371/journal.pone.0086313 |
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