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Population Pharmacokinetic/Pharmacodynamic Model-Guided Dosing Optimization of a Novel Sedative HR7056 in Chinese Healthy Subjects
HR7056 is a new benzodiazepine, showing more faster acting onset and recovery than currently available short-acting sedatives. To avoid inadequate anesthesia and predict return of cognition, allowing for immediate neurological evaluation, HR7056 pharmacokinetics and pharmacodynamics were characteriz...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252322/ https://www.ncbi.nlm.nih.gov/pubmed/30510509 http://dx.doi.org/10.3389/fphar.2018.01316 |
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author | Zhou, Ying Hu, Pei Huang, Yuguang Sang, Nuoer Song, Kaicheng Wang, Hongyun Wen, Jinhua Jiang, Ji Chen, Xia |
author_facet | Zhou, Ying Hu, Pei Huang, Yuguang Sang, Nuoer Song, Kaicheng Wang, Hongyun Wen, Jinhua Jiang, Ji Chen, Xia |
author_sort | Zhou, Ying |
collection | PubMed |
description | HR7056 is a new benzodiazepine, showing more faster acting onset and recovery than currently available short-acting sedatives. To avoid inadequate anesthesia and predict return of cognition, allowing for immediate neurological evaluation, HR7056 pharmacokinetics and pharmacodynamics were characterized in Chinese healthy subjects. We report on modeling of the data and simulations of dosage regimens for future study. Up to 63 subjects were evaluated, using Bispectral Index (BIS) and Modified Observer's Assessment of Alertness/Sedation (MOAA/S) as pharmacodynamics endpoints. A three-compartment model best described HR7056 pharmacokinetics. Total clearance was 1.49 L min(−1), central volume was 2.1 L, inter-compartmental clearances were 0.96 and 0.27 L min(−1), respectively. The population mean pharmacodynamic parameters were as follows: BIS, E(0): 95.3; IC(50): 503 ng mL(−1); γ: 1.5; k(e0): 0.0855 min(−1); I(max): 47.9 and MOAA/S, IC(50): 436 ng mL(−1); γ: 1.5; k(e0): 0.05 min(−1); I(max): 27.9. The model simulation will enable maintenance doses to be given more accurately for future study. Clinical Trial Registration: identifier: NCT01970072 |
format | Online Article Text |
id | pubmed-6252322 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-62523222018-12-03 Population Pharmacokinetic/Pharmacodynamic Model-Guided Dosing Optimization of a Novel Sedative HR7056 in Chinese Healthy Subjects Zhou, Ying Hu, Pei Huang, Yuguang Sang, Nuoer Song, Kaicheng Wang, Hongyun Wen, Jinhua Jiang, Ji Chen, Xia Front Pharmacol Pharmacology HR7056 is a new benzodiazepine, showing more faster acting onset and recovery than currently available short-acting sedatives. To avoid inadequate anesthesia and predict return of cognition, allowing for immediate neurological evaluation, HR7056 pharmacokinetics and pharmacodynamics were characterized in Chinese healthy subjects. We report on modeling of the data and simulations of dosage regimens for future study. Up to 63 subjects were evaluated, using Bispectral Index (BIS) and Modified Observer's Assessment of Alertness/Sedation (MOAA/S) as pharmacodynamics endpoints. A three-compartment model best described HR7056 pharmacokinetics. Total clearance was 1.49 L min(−1), central volume was 2.1 L, inter-compartmental clearances were 0.96 and 0.27 L min(−1), respectively. The population mean pharmacodynamic parameters were as follows: BIS, E(0): 95.3; IC(50): 503 ng mL(−1); γ: 1.5; k(e0): 0.0855 min(−1); I(max): 47.9 and MOAA/S, IC(50): 436 ng mL(−1); γ: 1.5; k(e0): 0.05 min(−1); I(max): 27.9. The model simulation will enable maintenance doses to be given more accurately for future study. Clinical Trial Registration: identifier: NCT01970072 Frontiers Media S.A. 2018-11-19 /pmc/articles/PMC6252322/ /pubmed/30510509 http://dx.doi.org/10.3389/fphar.2018.01316 Text en Copyright © 2018 Zhou, Hu, Huang, Sang, Song, Wang, Wen, Jiang and Chen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Zhou, Ying Hu, Pei Huang, Yuguang Sang, Nuoer Song, Kaicheng Wang, Hongyun Wen, Jinhua Jiang, Ji Chen, Xia Population Pharmacokinetic/Pharmacodynamic Model-Guided Dosing Optimization of a Novel Sedative HR7056 in Chinese Healthy Subjects |
title | Population Pharmacokinetic/Pharmacodynamic Model-Guided Dosing Optimization of a Novel Sedative HR7056 in Chinese Healthy Subjects |
title_full | Population Pharmacokinetic/Pharmacodynamic Model-Guided Dosing Optimization of a Novel Sedative HR7056 in Chinese Healthy Subjects |
title_fullStr | Population Pharmacokinetic/Pharmacodynamic Model-Guided Dosing Optimization of a Novel Sedative HR7056 in Chinese Healthy Subjects |
title_full_unstemmed | Population Pharmacokinetic/Pharmacodynamic Model-Guided Dosing Optimization of a Novel Sedative HR7056 in Chinese Healthy Subjects |
title_short | Population Pharmacokinetic/Pharmacodynamic Model-Guided Dosing Optimization of a Novel Sedative HR7056 in Chinese Healthy Subjects |
title_sort | population pharmacokinetic/pharmacodynamic model-guided dosing optimization of a novel sedative hr7056 in chinese healthy subjects |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252322/ https://www.ncbi.nlm.nih.gov/pubmed/30510509 http://dx.doi.org/10.3389/fphar.2018.01316 |
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