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, tw...
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Frontiers Media S.A.
2017-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fphar.2017.00636/full |
| _version_ | 1811259679453478912 |
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| author | Lulu Chen Lulu Chen Luping Zhou Luping Zhou Yaqin Wang Yaqin Wang Guoping Yang Jie Huang Zhirong Tan Zhirong Tan Yicheng Wang Yicheng Wang Gan Zhou Gan Zhou Jianwei Liao Jianwei Liao Dongsheng Ouyang Dongsheng Ouyang |
| author_facet | Lulu Chen Lulu Chen Luping Zhou Luping Zhou Yaqin Wang Yaqin Wang Guoping Yang Jie Huang Zhirong Tan Zhirong Tan Yicheng Wang Yicheng Wang Gan Zhou Gan Zhou Jianwei Liao Jianwei Liao Dongsheng Ouyang Dongsheng Ouyang |
| author_sort | Lulu Chen |
| collection | DOAJ |
| 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 tmax being shortened from 3.6 to 2.5 h (p = 0.015). In contrast, food significantly increased the Cmax, AUClast, and AUCinf(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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| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-12T18:35:10Z |
| publishDate | 2017-09-01 |
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| spelling | doaj.art-bf103434b2e948849a8c563be0c3b3332022-12-22T03:20:58ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122017-09-01810.3389/fphar.2017.00636285472Food and Sex-Related Impacts on the Pharmacokinetics of a Single-Dose of Ginsenoside Compound K in Healthy SubjectsLulu Chen0Lulu Chen1Luping Zhou2Luping Zhou3Yaqin Wang4Yaqin Wang5Guoping Yang6Jie Huang7Zhirong Tan8Zhirong Tan9Yicheng Wang10Yicheng Wang11Gan Zhou12Gan Zhou13Jianwei Liao14Jianwei Liao15Dongsheng Ouyang16Dongsheng Ouyang17Department of Clinical Pharmacology, Xiangya Hospital Central South UniversityChangsha, ChinaInstitute of Clinical Pharmacology, Central South UniversityChangsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital Central South UniversityChangsha, ChinaInstitute of Clinical Pharmacology, Central South UniversityChangsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital Central South UniversityChangsha, ChinaInstitute of Clinical Pharmacology, Central South UniversityChangsha, ChinaCenter of Clinical Pharmacology, The Third Xiangya Hospital, Central South UniversityChangsha, ChinaCenter of Clinical Pharmacology, The Third Xiangya Hospital, Central South UniversityChangsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital Central South UniversityChangsha, ChinaInstitute of Clinical Pharmacology, Central South UniversityChangsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital Central South UniversityChangsha, ChinaInstitute of Clinical Pharmacology, Central South UniversityChangsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital Central South UniversityChangsha, ChinaInstitute of Clinical Pharmacology, Central South UniversityChangsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital Central South UniversityChangsha, ChinaInstitute of Clinical Pharmacology, Central South UniversityChangsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital Central South UniversityChangsha, ChinaInstitute of Clinical Pharmacology, Central South UniversityChangsha, ChinaBackground 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 tmax being shortened from 3.6 to 2.5 h (p = 0.015). In contrast, food significantly increased the Cmax, AUClast, and AUCinf(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.http://journal.frontiersin.org/article/10.3389/fphar.2017.00636/fullclinical trialfood effectsex effectginsenosides compound KpharmacokineticsChiCTR-IPR-15005787 |
| spellingShingle | Lulu Chen Lulu Chen Luping Zhou Luping Zhou Yaqin Wang Yaqin Wang Guoping Yang Jie Huang Zhirong Tan Zhirong Tan Yicheng Wang Yicheng Wang Gan Zhou Gan Zhou Jianwei Liao Jianwei Liao Dongsheng Ouyang Dongsheng Ouyang Food and Sex-Related Impacts on the Pharmacokinetics of a Single-Dose of Ginsenoside Compound K in Healthy Subjects Frontiers in Pharmacology clinical trial food effect sex effect ginsenosides compound K pharmacokinetics ChiCTR-IPR-15005787 |
| 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 | clinical trial food effect sex effect ginsenosides compound K pharmacokinetics ChiCTR-IPR-15005787 |
| url | http://journal.frontiersin.org/article/10.3389/fphar.2017.00636/full |
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