Safety, Pharmacokinetics/Pharmacodynamics, and Absolute Bioavailability of Dexmedetomidine Hydrochloride Nasal Spray in Healthy Subjects: A Randomized, Parallel, Escalating Dose Study

Background: The present study evaluated the safety, pharmacokinetics/pharmacodynamics (PK/PD), and absolute bioavailability (Fabs) of Dex nasal spray in healthy adult subjects, which serves as a bridge for the subsequent study in children.Methods: Part 1: a double-blind, placebo-controlled, single a...
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Autor*in:	Yun Kuang [verfasserIn] Sai-Ying Wang [verfasserIn] Meng-Na Wang [verfasserIn] Guo-Ping Yang [verfasserIn] Can Guo [verfasserIn] Shuang Yang [verfasserIn] Xing-Fei Zhang [verfasserIn] Xiao-Yan Yang [verfasserIn] Qi Pei [verfasserIn] Chan Zou [verfasserIn] Yan-Hong He [verfasserIn] Ying-Yong Zhou [verfasserIn] Kai-Ming Duan [verfasserIn] Jie Huang [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	dexmedetomidine nasal spray pharmacokinetics pharmacodynamics absolute bioavailability healthy subjects

Übergeordnetes Werk:	In: Frontiers in Pharmacology - Frontiers Media S.A., 2010, 13(2022)
Übergeordnetes Werk:	volume:13 ; year:2022

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fphar.2022.871492

Katalog-ID:	DOAJ028135385

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245	1	0	\|a Safety, Pharmacokinetics/Pharmacodynamics, and Absolute Bioavailability of Dexmedetomidine Hydrochloride Nasal Spray in Healthy Subjects: A Randomized, Parallel, Escalating Dose Study
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520			\|a Background: The present study evaluated the safety, pharmacokinetics/pharmacodynamics (PK/PD), and absolute bioavailability (Fabs) of Dex nasal spray in healthy adult subjects, which serves as a bridge for the subsequent study in children.Methods: Part 1: a double-blind, placebo-controlled, single ascending dose study was performed on 48 subjects. For 20-/40-μg groups, every 6/2 subjects received either Dex/placebo nasal spray or Dex/placebo injection in two periods. In total, 12/4 subjects each received 100 μg Dex/placebo nasal spray. Part 2: a randomized, double-blind, placebo-controlled study; 12/4 subjects received 150 μg Dex/placebo nasal spray. Part 3: a randomized, open, self-crossover study; 12 subjects received 20 μg and 100 μg Dex nasal spray in two periods alternately. The method of administration was optimized in Part 2 and Part 3.Results: In part 1, Dex nasal spray was well tolerated up to the maximum dose of 100 μg, whereas the Fabs was tolerated to only 28.9%–32.3%. In Part 2 and Part 3, the optimized nasal spray method was adopted to promote the Fabs of Dex nasal spray to 74.1%–89.0%. A severe adverse event was found in Part 2. In Part 3 (100 μg), the Ramsay score increased the most and lasted the longest, whereas the BIS score decreased most significantly.Conclusion: Using the optimized nasal spray method, a single dose of 20/100 μg of the test drug was safe and tolerable, and 100 μg may have approached or reached the plateau of sedation. In addition, it is found that the optimized method can greatly improve the bioavailability of the test drug, leading to its higher reference value.
650		4	\|a dexmedetomidine nasal spray
650		4	\|a pharmacokinetics
650		4	\|a pharmacodynamics
650		4	\|a absolute bioavailability
650		4	\|a healthy subjects
653		0	\|a Therapeutics. Pharmacology
700	0		\|a Sai-Ying Wang \|e verfasserin \|4 aut
700	0		\|a Meng-Na Wang \|e verfasserin \|4 aut
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700	0		\|a Guo-Ping Yang \|e verfasserin \|4 aut
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700	0		\|a Can Guo \|e verfasserin \|4 aut
700	0		\|a Shuang Yang \|e verfasserin \|4 aut
700	0		\|a Xing-Fei Zhang \|e verfasserin \|4 aut
700	0		\|a Xiao-Yan Yang \|e verfasserin \|4 aut
700	0		\|a Qi Pei \|e verfasserin \|4 aut
700	0		\|a Chan Zou \|e verfasserin \|4 aut
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700	0		\|a Yan-Hong He \|e verfasserin \|4 aut
700	0		\|a Ying-Yong Zhou \|e verfasserin \|4 aut
700	0		\|a Kai-Ming Duan \|e verfasserin \|4 aut
700	0		\|a Jie Huang \|e verfasserin \|4 aut
700	0		\|a Jie Huang \|e verfasserin \|4 aut
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allfields	10.3389/fphar.2022.871492 doi (DE-627)DOAJ028135385 (DE-599)DOAJa75377148947426095d0f0bafe4b7da9 DE-627 ger DE-627 rakwb eng RM1-950 Yun Kuang verfasserin aut Safety, Pharmacokinetics/Pharmacodynamics, and Absolute Bioavailability of Dexmedetomidine Hydrochloride Nasal Spray in Healthy Subjects: A Randomized, Parallel, Escalating Dose Study 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: The present study evaluated the safety, pharmacokinetics/pharmacodynamics (PK/PD), and absolute bioavailability (Fabs) of Dex nasal spray in healthy adult subjects, which serves as a bridge for the subsequent study in children.Methods: Part 1: a double-blind, placebo-controlled, single ascending dose study was performed on 48 subjects. For 20-/40-μg groups, every 6/2 subjects received either Dex/placebo nasal spray or Dex/placebo injection in two periods. In total, 12/4 subjects each received 100 μg Dex/placebo nasal spray. Part 2: a randomized, double-blind, placebo-controlled study; 12/4 subjects received 150 μg Dex/placebo nasal spray. Part 3: a randomized, open, self-crossover study; 12 subjects received 20 μg and 100 μg Dex nasal spray in two periods alternately. The method of administration was optimized in Part 2 and Part 3.Results: In part 1, Dex nasal spray was well tolerated up to the maximum dose of 100 μg, whereas the Fabs was tolerated to only 28.9%–32.3%. In Part 2 and Part 3, the optimized nasal spray method was adopted to promote the Fabs of Dex nasal spray to 74.1%–89.0%. A severe adverse event was found in Part 2. In Part 3 (100 μg), the Ramsay score increased the most and lasted the longest, whereas the BIS score decreased most significantly.Conclusion: Using the optimized nasal spray method, a single dose of 20/100 μg of the test drug was safe and tolerable, and 100 μg may have approached or reached the plateau of sedation. In addition, it is found that the optimized method can greatly improve the bioavailability of the test drug, leading to its higher reference value. dexmedetomidine nasal spray pharmacokinetics pharmacodynamics absolute bioavailability healthy subjects Therapeutics. Pharmacology Sai-Ying Wang verfasserin aut Meng-Na Wang verfasserin aut Guo-Ping Yang verfasserin aut Guo-Ping Yang verfasserin aut Guo-Ping Yang verfasserin aut Can Guo verfasserin aut Shuang Yang verfasserin aut Xing-Fei Zhang verfasserin aut Xiao-Yan Yang verfasserin aut Qi Pei verfasserin aut Chan Zou verfasserin aut Chan Zou verfasserin aut Yan-Hong He verfasserin aut Ying-Yong Zhou verfasserin aut Kai-Ming Duan verfasserin aut Jie Huang verfasserin aut Jie Huang verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 13(2022) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:13 year:2022 https://doi.org/10.3389/fphar.2022.871492 kostenfrei https://doaj.org/article/a75377148947426095d0f0bafe4b7da9 kostenfrei https://www.frontiersin.org/articles/10.3389/fphar.2022.871492/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022
spelling	10.3389/fphar.2022.871492 doi (DE-627)DOAJ028135385 (DE-599)DOAJa75377148947426095d0f0bafe4b7da9 DE-627 ger DE-627 rakwb eng RM1-950 Yun Kuang verfasserin aut Safety, Pharmacokinetics/Pharmacodynamics, and Absolute Bioavailability of Dexmedetomidine Hydrochloride Nasal Spray in Healthy Subjects: A Randomized, Parallel, Escalating Dose Study 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: The present study evaluated the safety, pharmacokinetics/pharmacodynamics (PK/PD), and absolute bioavailability (Fabs) of Dex nasal spray in healthy adult subjects, which serves as a bridge for the subsequent study in children.Methods: Part 1: a double-blind, placebo-controlled, single ascending dose study was performed on 48 subjects. For 20-/40-μg groups, every 6/2 subjects received either Dex/placebo nasal spray or Dex/placebo injection in two periods. In total, 12/4 subjects each received 100 μg Dex/placebo nasal spray. Part 2: a randomized, double-blind, placebo-controlled study; 12/4 subjects received 150 μg Dex/placebo nasal spray. Part 3: a randomized, open, self-crossover study; 12 subjects received 20 μg and 100 μg Dex nasal spray in two periods alternately. The method of administration was optimized in Part 2 and Part 3.Results: In part 1, Dex nasal spray was well tolerated up to the maximum dose of 100 μg, whereas the Fabs was tolerated to only 28.9%–32.3%. In Part 2 and Part 3, the optimized nasal spray method was adopted to promote the Fabs of Dex nasal spray to 74.1%–89.0%. A severe adverse event was found in Part 2. In Part 3 (100 μg), the Ramsay score increased the most and lasted the longest, whereas the BIS score decreased most significantly.Conclusion: Using the optimized nasal spray method, a single dose of 20/100 μg of the test drug was safe and tolerable, and 100 μg may have approached or reached the plateau of sedation. In addition, it is found that the optimized method can greatly improve the bioavailability of the test drug, leading to its higher reference value. dexmedetomidine nasal spray pharmacokinetics pharmacodynamics absolute bioavailability healthy subjects Therapeutics. Pharmacology Sai-Ying Wang verfasserin aut Meng-Na Wang verfasserin aut Guo-Ping Yang verfasserin aut Guo-Ping Yang verfasserin aut Guo-Ping Yang verfasserin aut Can Guo verfasserin aut Shuang Yang verfasserin aut Xing-Fei Zhang verfasserin aut Xiao-Yan Yang verfasserin aut Qi Pei verfasserin aut Chan Zou verfasserin aut Chan Zou verfasserin aut Yan-Hong He verfasserin aut Ying-Yong Zhou verfasserin aut Kai-Ming Duan verfasserin aut Jie Huang verfasserin aut Jie Huang verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 13(2022) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:13 year:2022 https://doi.org/10.3389/fphar.2022.871492 kostenfrei https://doaj.org/article/a75377148947426095d0f0bafe4b7da9 kostenfrei https://www.frontiersin.org/articles/10.3389/fphar.2022.871492/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022
allfields_unstemmed	10.3389/fphar.2022.871492 doi (DE-627)DOAJ028135385 (DE-599)DOAJa75377148947426095d0f0bafe4b7da9 DE-627 ger DE-627 rakwb eng RM1-950 Yun Kuang verfasserin aut Safety, Pharmacokinetics/Pharmacodynamics, and Absolute Bioavailability of Dexmedetomidine Hydrochloride Nasal Spray in Healthy Subjects: A Randomized, Parallel, Escalating Dose Study 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: The present study evaluated the safety, pharmacokinetics/pharmacodynamics (PK/PD), and absolute bioavailability (Fabs) of Dex nasal spray in healthy adult subjects, which serves as a bridge for the subsequent study in children.Methods: Part 1: a double-blind, placebo-controlled, single ascending dose study was performed on 48 subjects. For 20-/40-μg groups, every 6/2 subjects received either Dex/placebo nasal spray or Dex/placebo injection in two periods. In total, 12/4 subjects each received 100 μg Dex/placebo nasal spray. Part 2: a randomized, double-blind, placebo-controlled study; 12/4 subjects received 150 μg Dex/placebo nasal spray. Part 3: a randomized, open, self-crossover study; 12 subjects received 20 μg and 100 μg Dex nasal spray in two periods alternately. The method of administration was optimized in Part 2 and Part 3.Results: In part 1, Dex nasal spray was well tolerated up to the maximum dose of 100 μg, whereas the Fabs was tolerated to only 28.9%–32.3%. In Part 2 and Part 3, the optimized nasal spray method was adopted to promote the Fabs of Dex nasal spray to 74.1%–89.0%. A severe adverse event was found in Part 2. In Part 3 (100 μg), the Ramsay score increased the most and lasted the longest, whereas the BIS score decreased most significantly.Conclusion: Using the optimized nasal spray method, a single dose of 20/100 μg of the test drug was safe and tolerable, and 100 μg may have approached or reached the plateau of sedation. In addition, it is found that the optimized method can greatly improve the bioavailability of the test drug, leading to its higher reference value. dexmedetomidine nasal spray pharmacokinetics pharmacodynamics absolute bioavailability healthy subjects Therapeutics. Pharmacology Sai-Ying Wang verfasserin aut Meng-Na Wang verfasserin aut Guo-Ping Yang verfasserin aut Guo-Ping Yang verfasserin aut Guo-Ping Yang verfasserin aut Can Guo verfasserin aut Shuang Yang verfasserin aut Xing-Fei Zhang verfasserin aut Xiao-Yan Yang verfasserin aut Qi Pei verfasserin aut Chan Zou verfasserin aut Chan Zou verfasserin aut Yan-Hong He verfasserin aut Ying-Yong Zhou verfasserin aut Kai-Ming Duan verfasserin aut Jie Huang verfasserin aut Jie Huang verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 13(2022) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:13 year:2022 https://doi.org/10.3389/fphar.2022.871492 kostenfrei https://doaj.org/article/a75377148947426095d0f0bafe4b7da9 kostenfrei https://www.frontiersin.org/articles/10.3389/fphar.2022.871492/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022
allfieldsGer	10.3389/fphar.2022.871492 doi (DE-627)DOAJ028135385 (DE-599)DOAJa75377148947426095d0f0bafe4b7da9 DE-627 ger DE-627 rakwb eng RM1-950 Yun Kuang verfasserin aut Safety, Pharmacokinetics/Pharmacodynamics, and Absolute Bioavailability of Dexmedetomidine Hydrochloride Nasal Spray in Healthy Subjects: A Randomized, Parallel, Escalating Dose Study 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: The present study evaluated the safety, pharmacokinetics/pharmacodynamics (PK/PD), and absolute bioavailability (Fabs) of Dex nasal spray in healthy adult subjects, which serves as a bridge for the subsequent study in children.Methods: Part 1: a double-blind, placebo-controlled, single ascending dose study was performed on 48 subjects. For 20-/40-μg groups, every 6/2 subjects received either Dex/placebo nasal spray or Dex/placebo injection in two periods. In total, 12/4 subjects each received 100 μg Dex/placebo nasal spray. Part 2: a randomized, double-blind, placebo-controlled study; 12/4 subjects received 150 μg Dex/placebo nasal spray. Part 3: a randomized, open, self-crossover study; 12 subjects received 20 μg and 100 μg Dex nasal spray in two periods alternately. The method of administration was optimized in Part 2 and Part 3.Results: In part 1, Dex nasal spray was well tolerated up to the maximum dose of 100 μg, whereas the Fabs was tolerated to only 28.9%–32.3%. In Part 2 and Part 3, the optimized nasal spray method was adopted to promote the Fabs of Dex nasal spray to 74.1%–89.0%. A severe adverse event was found in Part 2. In Part 3 (100 μg), the Ramsay score increased the most and lasted the longest, whereas the BIS score decreased most significantly.Conclusion: Using the optimized nasal spray method, a single dose of 20/100 μg of the test drug was safe and tolerable, and 100 μg may have approached or reached the plateau of sedation. In addition, it is found that the optimized method can greatly improve the bioavailability of the test drug, leading to its higher reference value. dexmedetomidine nasal spray pharmacokinetics pharmacodynamics absolute bioavailability healthy subjects Therapeutics. Pharmacology Sai-Ying Wang verfasserin aut Meng-Na Wang verfasserin aut Guo-Ping Yang verfasserin aut Guo-Ping Yang verfasserin aut Guo-Ping Yang verfasserin aut Can Guo verfasserin aut Shuang Yang verfasserin aut Xing-Fei Zhang verfasserin aut Xiao-Yan Yang verfasserin aut Qi Pei verfasserin aut Chan Zou verfasserin aut Chan Zou verfasserin aut Yan-Hong He verfasserin aut Ying-Yong Zhou verfasserin aut Kai-Ming Duan verfasserin aut Jie Huang verfasserin aut Jie Huang verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 13(2022) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:13 year:2022 https://doi.org/10.3389/fphar.2022.871492 kostenfrei https://doaj.org/article/a75377148947426095d0f0bafe4b7da9 kostenfrei https://www.frontiersin.org/articles/10.3389/fphar.2022.871492/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022
allfieldsSound	10.3389/fphar.2022.871492 doi (DE-627)DOAJ028135385 (DE-599)DOAJa75377148947426095d0f0bafe4b7da9 DE-627 ger DE-627 rakwb eng RM1-950 Yun Kuang verfasserin aut Safety, Pharmacokinetics/Pharmacodynamics, and Absolute Bioavailability of Dexmedetomidine Hydrochloride Nasal Spray in Healthy Subjects: A Randomized, Parallel, Escalating Dose Study 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: The present study evaluated the safety, pharmacokinetics/pharmacodynamics (PK/PD), and absolute bioavailability (Fabs) of Dex nasal spray in healthy adult subjects, which serves as a bridge for the subsequent study in children.Methods: Part 1: a double-blind, placebo-controlled, single ascending dose study was performed on 48 subjects. For 20-/40-μg groups, every 6/2 subjects received either Dex/placebo nasal spray or Dex/placebo injection in two periods. In total, 12/4 subjects each received 100 μg Dex/placebo nasal spray. Part 2: a randomized, double-blind, placebo-controlled study; 12/4 subjects received 150 μg Dex/placebo nasal spray. Part 3: a randomized, open, self-crossover study; 12 subjects received 20 μg and 100 μg Dex nasal spray in two periods alternately. The method of administration was optimized in Part 2 and Part 3.Results: In part 1, Dex nasal spray was well tolerated up to the maximum dose of 100 μg, whereas the Fabs was tolerated to only 28.9%–32.3%. In Part 2 and Part 3, the optimized nasal spray method was adopted to promote the Fabs of Dex nasal spray to 74.1%–89.0%. A severe adverse event was found in Part 2. In Part 3 (100 μg), the Ramsay score increased the most and lasted the longest, whereas the BIS score decreased most significantly.Conclusion: Using the optimized nasal spray method, a single dose of 20/100 μg of the test drug was safe and tolerable, and 100 μg may have approached or reached the plateau of sedation. In addition, it is found that the optimized method can greatly improve the bioavailability of the test drug, leading to its higher reference value. dexmedetomidine nasal spray pharmacokinetics pharmacodynamics absolute bioavailability healthy subjects Therapeutics. Pharmacology Sai-Ying Wang verfasserin aut Meng-Na Wang verfasserin aut Guo-Ping Yang verfasserin aut Guo-Ping Yang verfasserin aut Guo-Ping Yang verfasserin aut Can Guo verfasserin aut Shuang Yang verfasserin aut Xing-Fei Zhang verfasserin aut Xiao-Yan Yang verfasserin aut Qi Pei verfasserin aut Chan Zou verfasserin aut Chan Zou verfasserin aut Yan-Hong He verfasserin aut Ying-Yong Zhou verfasserin aut Kai-Ming Duan verfasserin aut Jie Huang verfasserin aut Jie Huang verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 13(2022) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:13 year:2022 https://doi.org/10.3389/fphar.2022.871492 kostenfrei https://doaj.org/article/a75377148947426095d0f0bafe4b7da9 kostenfrei https://www.frontiersin.org/articles/10.3389/fphar.2022.871492/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022
language	English
source	In Frontiers in Pharmacology 13(2022) volume:13 year:2022
sourceStr	In Frontiers in Pharmacology 13(2022) volume:13 year:2022
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	dexmedetomidine nasal spray pharmacokinetics pharmacodynamics absolute bioavailability healthy subjects Therapeutics. Pharmacology
isfreeaccess_bool	true
container_title	Frontiers in Pharmacology
authorswithroles_txt_mv	Yun Kuang @@aut@@ Sai-Ying Wang @@aut@@ Meng-Na Wang @@aut@@ Guo-Ping Yang @@aut@@ Can Guo @@aut@@ Shuang Yang @@aut@@ Xing-Fei Zhang @@aut@@ Xiao-Yan Yang @@aut@@ Qi Pei @@aut@@ Chan Zou @@aut@@ Yan-Hong He @@aut@@ Ying-Yong Zhou @@aut@@ Kai-Ming Duan @@aut@@ Jie Huang @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
hierarchy_top_id	642889392
id	DOAJ028135385
language_de	englisch
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For 20-/40-μg groups, every 6/2 subjects received either Dex/placebo nasal spray or Dex/placebo injection in two periods. In total, 12/4 subjects each received 100 μg Dex/placebo nasal spray. Part 2: a randomized, double-blind, placebo-controlled study; 12/4 subjects received 150 μg Dex/placebo nasal spray. Part 3: a randomized, open, self-crossover study; 12 subjects received 20 μg and 100 μg Dex nasal spray in two periods alternately. The method of administration was optimized in Part 2 and Part 3.Results: In part 1, Dex nasal spray was well tolerated up to the maximum dose of 100 μg, whereas the Fabs was tolerated to only 28.9%–32.3%. In Part 2 and Part 3, the optimized nasal spray method was adopted to promote the Fabs of Dex nasal spray to 74.1%–89.0%. A severe adverse event was found in Part 2. In Part 3 (100 μg), the Ramsay score increased the most and lasted the longest, whereas the BIS score decreased most significantly.Conclusion: Using the optimized nasal spray method, a single dose of 20/100 μg of the test drug was safe and tolerable, and 100 μg may have approached or reached the plateau of sedation. 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callnumber-first	R - Medicine
author	Yun Kuang
spellingShingle	Yun Kuang misc RM1-950 misc dexmedetomidine nasal spray misc pharmacokinetics misc pharmacodynamics misc absolute bioavailability misc healthy subjects misc Therapeutics. Pharmacology Safety, Pharmacokinetics/Pharmacodynamics, and Absolute Bioavailability of Dexmedetomidine Hydrochloride Nasal Spray in Healthy Subjects: A Randomized, Parallel, Escalating Dose Study
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topic_title	RM1-950 Safety, Pharmacokinetics/Pharmacodynamics, and Absolute Bioavailability of Dexmedetomidine Hydrochloride Nasal Spray in Healthy Subjects: A Randomized, Parallel, Escalating Dose Study dexmedetomidine nasal spray pharmacokinetics pharmacodynamics absolute bioavailability healthy subjects
topic	misc RM1-950 misc dexmedetomidine nasal spray misc pharmacokinetics misc pharmacodynamics misc absolute bioavailability misc healthy subjects misc Therapeutics. Pharmacology
topic_unstemmed	misc RM1-950 misc dexmedetomidine nasal spray misc pharmacokinetics misc pharmacodynamics misc absolute bioavailability misc healthy subjects misc Therapeutics. Pharmacology
topic_browse	misc RM1-950 misc dexmedetomidine nasal spray misc pharmacokinetics misc pharmacodynamics misc absolute bioavailability misc healthy subjects misc Therapeutics. Pharmacology
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title	Safety, Pharmacokinetics/Pharmacodynamics, and Absolute Bioavailability of Dexmedetomidine Hydrochloride Nasal Spray in Healthy Subjects: A Randomized, Parallel, Escalating Dose Study
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title_full	Safety, Pharmacokinetics/Pharmacodynamics, and Absolute Bioavailability of Dexmedetomidine Hydrochloride Nasal Spray in Healthy Subjects: A Randomized, Parallel, Escalating Dose Study
author_sort	Yun Kuang
journal	Frontiers in Pharmacology
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author_browse	Yun Kuang Sai-Ying Wang Meng-Na Wang Guo-Ping Yang Can Guo Shuang Yang Xing-Fei Zhang Xiao-Yan Yang Qi Pei Chan Zou Yan-Hong He Ying-Yong Zhou Kai-Ming Duan Jie Huang
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doi_str_mv	10.3389/fphar.2022.871492
author2-role	verfasserin
title_sort	safety, pharmacokinetics/pharmacodynamics, and absolute bioavailability of dexmedetomidine hydrochloride nasal spray in healthy subjects: a randomized, parallel, escalating dose study
callnumber	RM1-950
title_auth	Safety, Pharmacokinetics/Pharmacodynamics, and Absolute Bioavailability of Dexmedetomidine Hydrochloride Nasal Spray in Healthy Subjects: A Randomized, Parallel, Escalating Dose Study
abstract	Background: The present study evaluated the safety, pharmacokinetics/pharmacodynamics (PK/PD), and absolute bioavailability (Fabs) of Dex nasal spray in healthy adult subjects, which serves as a bridge for the subsequent study in children.Methods: Part 1: a double-blind, placebo-controlled, single ascending dose study was performed on 48 subjects. For 20-/40-μg groups, every 6/2 subjects received either Dex/placebo nasal spray or Dex/placebo injection in two periods. In total, 12/4 subjects each received 100 μg Dex/placebo nasal spray. Part 2: a randomized, double-blind, placebo-controlled study; 12/4 subjects received 150 μg Dex/placebo nasal spray. Part 3: a randomized, open, self-crossover study; 12 subjects received 20 μg and 100 μg Dex nasal spray in two periods alternately. The method of administration was optimized in Part 2 and Part 3.Results: In part 1, Dex nasal spray was well tolerated up to the maximum dose of 100 μg, whereas the Fabs was tolerated to only 28.9%–32.3%. In Part 2 and Part 3, the optimized nasal spray method was adopted to promote the Fabs of Dex nasal spray to 74.1%–89.0%. A severe adverse event was found in Part 2. In Part 3 (100 μg), the Ramsay score increased the most and lasted the longest, whereas the BIS score decreased most significantly.Conclusion: Using the optimized nasal spray method, a single dose of 20/100 μg of the test drug was safe and tolerable, and 100 μg may have approached or reached the plateau of sedation. In addition, it is found that the optimized method can greatly improve the bioavailability of the test drug, leading to its higher reference value.
abstractGer	Background: The present study evaluated the safety, pharmacokinetics/pharmacodynamics (PK/PD), and absolute bioavailability (Fabs) of Dex nasal spray in healthy adult subjects, which serves as a bridge for the subsequent study in children.Methods: Part 1: a double-blind, placebo-controlled, single ascending dose study was performed on 48 subjects. For 20-/40-μg groups, every 6/2 subjects received either Dex/placebo nasal spray or Dex/placebo injection in two periods. In total, 12/4 subjects each received 100 μg Dex/placebo nasal spray. Part 2: a randomized, double-blind, placebo-controlled study; 12/4 subjects received 150 μg Dex/placebo nasal spray. Part 3: a randomized, open, self-crossover study; 12 subjects received 20 μg and 100 μg Dex nasal spray in two periods alternately. The method of administration was optimized in Part 2 and Part 3.Results: In part 1, Dex nasal spray was well tolerated up to the maximum dose of 100 μg, whereas the Fabs was tolerated to only 28.9%–32.3%. In Part 2 and Part 3, the optimized nasal spray method was adopted to promote the Fabs of Dex nasal spray to 74.1%–89.0%. A severe adverse event was found in Part 2. In Part 3 (100 μg), the Ramsay score increased the most and lasted the longest, whereas the BIS score decreased most significantly.Conclusion: Using the optimized nasal spray method, a single dose of 20/100 μg of the test drug was safe and tolerable, and 100 μg may have approached or reached the plateau of sedation. In addition, it is found that the optimized method can greatly improve the bioavailability of the test drug, leading to its higher reference value.
abstract_unstemmed	Background: The present study evaluated the safety, pharmacokinetics/pharmacodynamics (PK/PD), and absolute bioavailability (Fabs) of Dex nasal spray in healthy adult subjects, which serves as a bridge for the subsequent study in children.Methods: Part 1: a double-blind, placebo-controlled, single ascending dose study was performed on 48 subjects. For 20-/40-μg groups, every 6/2 subjects received either Dex/placebo nasal spray or Dex/placebo injection in two periods. In total, 12/4 subjects each received 100 μg Dex/placebo nasal spray. Part 2: a randomized, double-blind, placebo-controlled study; 12/4 subjects received 150 μg Dex/placebo nasal spray. Part 3: a randomized, open, self-crossover study; 12 subjects received 20 μg and 100 μg Dex nasal spray in two periods alternately. The method of administration was optimized in Part 2 and Part 3.Results: In part 1, Dex nasal spray was well tolerated up to the maximum dose of 100 μg, whereas the Fabs was tolerated to only 28.9%–32.3%. In Part 2 and Part 3, the optimized nasal spray method was adopted to promote the Fabs of Dex nasal spray to 74.1%–89.0%. A severe adverse event was found in Part 2. In Part 3 (100 μg), the Ramsay score increased the most and lasted the longest, whereas the BIS score decreased most significantly.Conclusion: Using the optimized nasal spray method, a single dose of 20/100 μg of the test drug was safe and tolerable, and 100 μg may have approached or reached the plateau of sedation. In addition, it is found that the optimized method can greatly improve the bioavailability of the test drug, leading to its higher reference value.
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title_short	Safety, Pharmacokinetics/Pharmacodynamics, and Absolute Bioavailability of Dexmedetomidine Hydrochloride Nasal Spray in Healthy Subjects: A Randomized, Parallel, Escalating Dose Study
url	https://doi.org/10.3389/fphar.2022.871492 https://doaj.org/article/a75377148947426095d0f0bafe4b7da9 https://www.frontiersin.org/articles/10.3389/fphar.2022.871492/full https://doaj.org/toc/1663-9812
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author2	Sai-Ying Wang Meng-Na Wang Guo-Ping Yang Can Guo Shuang Yang Xing-Fei Zhang Xiao-Yan Yang Qi Pei Chan Zou Yan-Hong He Ying-Yong Zhou Kai-Ming Duan Jie Huang
author2Str	Sai-Ying Wang Meng-Na Wang Guo-Ping Yang Can Guo Shuang Yang Xing-Fei Zhang Xiao-Yan Yang Qi Pei Chan Zou Yan-Hong He Ying-Yong Zhou Kai-Ming Duan Jie Huang
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up_date	2024-07-03T15:55:09.479Z
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Safety, Pharmacokinetics/Pharmacodynamics, and Absolute Bioavailability of Dexmedetomidine Hydrochloride Nasal Spray in Healthy Subjects: A Randomized, Parallel, Escalating Dose Study

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