Reduction in C-Peptide Levels and Influence on Pharmacokinetics and Pharmacodynamics of Insulin Preparations: How to Conduct a High-Quality Euglycemic Clamp Study

Objective: The aim of the study was to investigate the different extent of inhibition of endogenous insulin secretion by the reduction of C-peptide levels in an euglycemic clamp study and its effects on the evaluation of pharmacokinetics, pharmacodynamics of insulin preparations, and quality of clam...

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Autores principales:	Yi Tao, Mingxue Zhu, Junliang Pu, Peilin Zhang, Lei Wan, Chengyong Tang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	euglycemic clamp C-peptide glucose oscillation pharmacodynamics pharmacokinetics Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/b482d5d6737d4c9c9322a6a92c04a662
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spelling	oai:doaj.org-article:b482d5d6737d4c9c9322a6a92c04a6622021-12-02T11:16:41ZReduction in C-Peptide Levels and Influence on Pharmacokinetics and Pharmacodynamics of Insulin Preparations: How to Conduct a High-Quality Euglycemic Clamp Study1663-981210.3389/fphar.2021.786613https://doaj.org/article/b482d5d6737d4c9c9322a6a92c04a6622021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.786613/fullhttps://doaj.org/toc/1663-9812Objective: The aim of the study was to investigate the different extent of inhibition of endogenous insulin secretion by the reduction of C-peptide levels in an euglycemic clamp study and its effects on the evaluation of pharmacokinetics, pharmacodynamics of insulin preparations, and quality of clamp study to determine the best reduction range of C-peptide levels.Methods: Healthy Chinese male volunteers were enrolled and underwent a single-dose euglycemic clamp test. Participants were subcutaneously injected with long-acting insulin glargine (0.4 IU/kg). Blood samples were collected pretest and up to 24 h post-test to assess pharmacokinetics (PK), pharmacodynamics (PD), and C-peptide levels.Results: We divided the 39 volunteers enrolled in the study into three groups according to the reduction of C-peptide levels: group A (ratio of C-peptide reduction <30%, n = 13), group B (ratio of C-peptide reduction between ≥ 30% and <50%, n = 15), and group C (ratio of C-peptide reduction ≥50%, n = 11); there were significant differences in the three groups (p= 0.000). The upper and lower limits of blood glucose oscillation in group C was statistically lower than the other groups, the range of oscillating glucose levels in group C was −17.0 ± 6.6% to −1.1 ± 6.7%. The AUC0–24 h in groups A, B, and C were 9.7 ± 2.2, 11.0 ± 2.9, and 11.9 ± 2.1 ng/ml × min, respectively, which indicated an increasing trend in the three groups (Ptrend = 0.041). For quality assessment, the average glucose (p = 0.000) and MEFTG (p = 0.001) levels in three groups were significantly different.Conclusion: The different extent of inhibition of endogenous insulin will influence the PK/PD of insulin preparations and the quality of the euglycemic clamp. Furthermore, the ratio of C-peptide reduction should be above 50% to free from the interference of endogenous insulin, and the range of blood glucose levels should be consistently maintained at −10% to 0 in the euglycemic clamp.Yi TaoMingxue ZhuJunliang PuPeilin ZhangLei WanChengyong TangFrontiers Media S.A.articleeuglycemic clampC-peptideglucose oscillationpharmacodynamicspharmacokineticsTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	euglycemic clamp C-peptide glucose oscillation pharmacodynamics pharmacokinetics Therapeutics. Pharmacology RM1-950
spellingShingle	euglycemic clamp C-peptide glucose oscillation pharmacodynamics pharmacokinetics Therapeutics. Pharmacology RM1-950 Yi Tao Mingxue Zhu Junliang Pu Peilin Zhang Lei Wan Chengyong Tang Reduction in C-Peptide Levels and Influence on Pharmacokinetics and Pharmacodynamics of Insulin Preparations: How to Conduct a High-Quality Euglycemic Clamp Study
description	Objective: The aim of the study was to investigate the different extent of inhibition of endogenous insulin secretion by the reduction of C-peptide levels in an euglycemic clamp study and its effects on the evaluation of pharmacokinetics, pharmacodynamics of insulin preparations, and quality of clamp study to determine the best reduction range of C-peptide levels.Methods: Healthy Chinese male volunteers were enrolled and underwent a single-dose euglycemic clamp test. Participants were subcutaneously injected with long-acting insulin glargine (0.4 IU/kg). Blood samples were collected pretest and up to 24 h post-test to assess pharmacokinetics (PK), pharmacodynamics (PD), and C-peptide levels.Results: We divided the 39 volunteers enrolled in the study into three groups according to the reduction of C-peptide levels: group A (ratio of C-peptide reduction <30%, n = 13), group B (ratio of C-peptide reduction between ≥ 30% and <50%, n = 15), and group C (ratio of C-peptide reduction ≥50%, n = 11); there were significant differences in the three groups (p= 0.000). The upper and lower limits of blood glucose oscillation in group C was statistically lower than the other groups, the range of oscillating glucose levels in group C was −17.0 ± 6.6% to −1.1 ± 6.7%. The AUC0–24 h in groups A, B, and C were 9.7 ± 2.2, 11.0 ± 2.9, and 11.9 ± 2.1 ng/ml × min, respectively, which indicated an increasing trend in the three groups (Ptrend = 0.041). For quality assessment, the average glucose (p = 0.000) and MEFTG (p = 0.001) levels in three groups were significantly different.Conclusion: The different extent of inhibition of endogenous insulin will influence the PK/PD of insulin preparations and the quality of the euglycemic clamp. Furthermore, the ratio of C-peptide reduction should be above 50% to free from the interference of endogenous insulin, and the range of blood glucose levels should be consistently maintained at −10% to 0 in the euglycemic clamp.
format	article
author	Yi Tao Mingxue Zhu Junliang Pu Peilin Zhang Lei Wan Chengyong Tang
author_facet	Yi Tao Mingxue Zhu Junliang Pu Peilin Zhang Lei Wan Chengyong Tang
author_sort	Yi Tao
title	Reduction in C-Peptide Levels and Influence on Pharmacokinetics and Pharmacodynamics of Insulin Preparations: How to Conduct a High-Quality Euglycemic Clamp Study
title_short	Reduction in C-Peptide Levels and Influence on Pharmacokinetics and Pharmacodynamics of Insulin Preparations: How to Conduct a High-Quality Euglycemic Clamp Study
title_full	Reduction in C-Peptide Levels and Influence on Pharmacokinetics and Pharmacodynamics of Insulin Preparations: How to Conduct a High-Quality Euglycemic Clamp Study
title_fullStr	Reduction in C-Peptide Levels and Influence on Pharmacokinetics and Pharmacodynamics of Insulin Preparations: How to Conduct a High-Quality Euglycemic Clamp Study
title_full_unstemmed	Reduction in C-Peptide Levels and Influence on Pharmacokinetics and Pharmacodynamics of Insulin Preparations: How to Conduct a High-Quality Euglycemic Clamp Study
title_sort	reduction in c-peptide levels and influence on pharmacokinetics and pharmacodynamics of insulin preparations: how to conduct a high-quality euglycemic clamp study
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/b482d5d6737d4c9c9322a6a92c04a662
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Reduction in C-Peptide Levels and Influence on Pharmacokinetics and Pharmacodynamics of Insulin Preparations: How to Conduct a High-Quality Euglycemic Clamp Study

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