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Food and Sex-Related Impacts on the Pharmacokinetics of a Single-Dose of Ginsenoside Compound K in Healthy Subjects

Background and Objectives: Ginsenoside compound K (CK) is a candidate drug for rheumatoid arthritis therapy. This clinical trial was designed to evaluate the effects of food and sex on the pharmacokinetics of CK and its metabolite 20(S)-protopanaxadiol (PPD). Methods: An open-label, single-center, t...

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Autores principales: Chen, Lulu, Zhou, Luping, Wang, Yaqin, Yang, Guoping, Huang, Jie, Tan, Zhirong, Wang, Yicheng, Zhou, Gan, Liao, Jianwei, Ouyang, Dongsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602130/
https://www.ncbi.nlm.nih.gov/pubmed/28955238
http://dx.doi.org/10.3389/fphar.2017.00636
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author Chen, Lulu
Zhou, Luping
Wang, Yaqin
Yang, Guoping
Huang, Jie
Tan, Zhirong
Wang, Yicheng
Zhou, Gan
Liao, Jianwei
Ouyang, Dongsheng
author_facet Chen, Lulu
Zhou, Luping
Wang, Yaqin
Yang, Guoping
Huang, Jie
Tan, Zhirong
Wang, Yicheng
Zhou, Gan
Liao, Jianwei
Ouyang, Dongsheng
author_sort Chen, Lulu
collection PubMed
description Background and Objectives: Ginsenoside compound K (CK) is a candidate drug for rheumatoid arthritis therapy. This clinical trial was designed to evaluate the effects of food and sex on the pharmacokinetics of CK and its metabolite 20(S)-protopanaxadiol (PPD). Methods: An open-label, single-center, two-period crossover trial was performed in healthy Chinese subjects (n = 24; male = 12, female = 12), randomized to either the fasting overnight or the high-fat meal group before a single 200 mg dose of monomer CK was administered. According to the concentration-time data of plasma and urine samples from each subject, the pharmacokinetic parameters of CK and 20(S)-PPD were calculated and statistically analyzed. Results: A two-way ANOVA test combined with mean plots showed no statistically significant interaction between food and sex. High-fat meal accelerated the absorption of CK, with t(max) being shortened from 3.6 to 2.5 h (p = 0.015). In contrast, food significantly increased the C(max), AUC(last), and AUC(inf)(p < 0.001) with the 90% confidence intervals falling outside of the conventional 0.80–1.25. Females had higher exposure levels of CK than males, but the difference was statistically significant only after a high-fat meal. Of note, CK was rarely excreted in urine. Furthermore, the effects of food and sex were also observed on 20(S)-PPD. Conclusion: High-fat food and sex both had an impact on the disposition of CK in vivo, but rather than a significant interaction effect. High-fat food accelerated and increased the absorption of CK, while the exposure of CK was higher in females compared to males. The results indicate that food and sex should be two noteworthy factors in future research on CK.
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spelling pubmed-56021302017-09-27 Food and Sex-Related Impacts on the Pharmacokinetics of a Single-Dose of Ginsenoside Compound K in Healthy Subjects Chen, Lulu Zhou, Luping Wang, Yaqin Yang, Guoping Huang, Jie Tan, Zhirong Wang, Yicheng Zhou, Gan Liao, Jianwei Ouyang, Dongsheng Front Pharmacol Pharmacology Background and Objectives: Ginsenoside compound K (CK) is a candidate drug for rheumatoid arthritis therapy. This clinical trial was designed to evaluate the effects of food and sex on the pharmacokinetics of CK and its metabolite 20(S)-protopanaxadiol (PPD). Methods: An open-label, single-center, two-period crossover trial was performed in healthy Chinese subjects (n = 24; male = 12, female = 12), randomized to either the fasting overnight or the high-fat meal group before a single 200 mg dose of monomer CK was administered. According to the concentration-time data of plasma and urine samples from each subject, the pharmacokinetic parameters of CK and 20(S)-PPD were calculated and statistically analyzed. Results: A two-way ANOVA test combined with mean plots showed no statistically significant interaction between food and sex. High-fat meal accelerated the absorption of CK, with t(max) being shortened from 3.6 to 2.5 h (p = 0.015). In contrast, food significantly increased the C(max), AUC(last), and AUC(inf)(p < 0.001) with the 90% confidence intervals falling outside of the conventional 0.80–1.25. Females had higher exposure levels of CK than males, but the difference was statistically significant only after a high-fat meal. Of note, CK was rarely excreted in urine. Furthermore, the effects of food and sex were also observed on 20(S)-PPD. Conclusion: High-fat food and sex both had an impact on the disposition of CK in vivo, but rather than a significant interaction effect. High-fat food accelerated and increased the absorption of CK, while the exposure of CK was higher in females compared to males. The results indicate that food and sex should be two noteworthy factors in future research on CK. Frontiers Media S.A. 2017-09-13 /pmc/articles/PMC5602130/ /pubmed/28955238 http://dx.doi.org/10.3389/fphar.2017.00636 Text en Copyright © 2017 Chen, Zhou, Wang, Yang, Huang, Tan, Wang, Zhou, Liao and Ouyang. 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) or licensor 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
Chen, Lulu
Zhou, Luping
Wang, Yaqin
Yang, Guoping
Huang, Jie
Tan, Zhirong
Wang, Yicheng
Zhou, Gan
Liao, Jianwei
Ouyang, Dongsheng
Food and Sex-Related Impacts on the Pharmacokinetics of a Single-Dose of Ginsenoside Compound K in Healthy Subjects
title Food and Sex-Related Impacts on the Pharmacokinetics of a Single-Dose of Ginsenoside Compound K in Healthy Subjects
title_full Food and Sex-Related Impacts on the Pharmacokinetics of a Single-Dose of Ginsenoside Compound K in Healthy Subjects
title_fullStr Food and Sex-Related Impacts on the Pharmacokinetics of a Single-Dose of Ginsenoside Compound K in Healthy Subjects
title_full_unstemmed Food and Sex-Related Impacts on the Pharmacokinetics of a Single-Dose of Ginsenoside Compound K in Healthy Subjects
title_short Food and Sex-Related Impacts on the Pharmacokinetics of a Single-Dose of Ginsenoside Compound K in Healthy Subjects
title_sort food and sex-related impacts on the pharmacokinetics of a single-dose of ginsenoside compound k in healthy subjects
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602130/
https://www.ncbi.nlm.nih.gov/pubmed/28955238
http://dx.doi.org/10.3389/fphar.2017.00636
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