Ticagrelor and gut microbiota: Absence of pharmacokinetic interaction in vitro and in vivo studies
5 affiliations
- 1Engineering Research Center of Applied Technology of Pharmacogenomics (Ministry of Education, China), Hunan Key Laboratory of Pharmacomicrobiomics, Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
- 2Department of Pharmacy, Hunan Prevention and Treatment Institute for Occupational Diseases, Affiliated Prevention and Treatment Institute for Occupational Diseases of University of South China, Changsha, China
- 3The First Affiliated Hospital of Shantou University Medical College, Shantou, China
- 4Department of Pharmacy, Hunan Provincial People's Hospital, the First Affiliated Hospital of Hunan Normal University, Changsha, China
- 5Department of Cardiovascular, Xiangya Hospital, Central South University, Changsha, China
Abstract
Ticagrelor, a commonly used antiplatelet medication, has been found to exhibit considerable inter-individual pharmacodynamic variability. Recent studies have revealed a close relationship between pharmacokinetics and pharmacodynamics, both of which can be influenced by gut microbiota. In this study, we explored whether the pharmacokinetics of ticagrelor is mediated by intestinal flora. We enrolled 22 healthy participants to assess the clinical pharmacokinetic profiles of ticagrelor and its metabolite AR-C124910XX after a single oral dose of ticagrelor. The fecal microbial compositions of individuals who exhibited distinct pharmacokinetic parameters were analyzed using 16S rRNA gene sequencing. Additionally, we conducted experiments involving the co-incubation of ticagrelor with fecal bacteria and a systematic exploration of the pharmacokinetics of ticagrelor in pseudo-germ-free (PGF) rats to illustrate the role of gut microbiota in ticagrelor metabolism, both in vitro and in vivo. Our findings revealed a three-fold difference in the bioavailability of ticagrelor among individuals. However, no difference was found in the composition of gut microbiota among individuals with different pharmacokinetic parameters. Quantitative analysis showed that gut microbiota cannot directly metabolize ticagrelor. Furthermore, there were no significant differences in AUC(0–48), AUC(0-∞), and Cmax between ticagrelor and AR-C124910XX in PGF rats compared to normal control, either by single intragastric or intravenous administration. In conclusion, these findings suggest that gut microbiota has no impact on the pharmacokinetics of ticagrelor.
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BibTeX
@article{qu2026ticagrelor,
title = {{Ticagrelor and gut microbiota: Absence of pharmacokinetic interaction in vitro and in vivo studies}},
author = {Pan Qu and Yongchao Gao and Xiaojie Li and Li Yang and Jie Tang and Manyun Chen and Yicheng Wang and Yilei Peng and Junyi Jiang and Weihua Huang and Wei Zhang and Yali Liu and Yali Ou},
journal = {PLOS One},
year = {2026},
month = oct,
doi = {10.1371/journal.pone.0359660},
url = {https://doi.org/10.1371/journal.pone.0359660},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Ticagrelor and gut microbiota: Absence of pharmacokinetic interaction in vitro and in vivo studies
AU - Pan Qu
AU - Yongchao Gao
AU - Xiaojie Li
AU - Li Yang
AU - Jie Tang
AU - Manyun Chen
AU - Yicheng Wang
AU - Yilei Peng
AU - Junyi Jiang
AU - Weihua Huang
AU - Wei Zhang
AU - Yali Liu
AU - Yali Ou
PY - 2026
DA - 2026/10/01
JO - PLOS One
DO - 10.1371/journal.pone.0359660
UR - https://doi.org/10.1371/journal.pone.0359660
AB - Ticagrelor, a commonly used antiplatelet medication, has been found to exhibit considerable inter-individual pharmacodynamic variability. Recent studies have revealed a close relationship between pharmacokinetics and pharmacodynamics, both of which can be influenced by gut microbiota. In this study, we explored whether the pharmacokinetics of ticagrelor is mediated by intestinal flora. We enrolled 22 healthy participants to assess the clinical pharmacokinetic profiles of ticagrelor and its metabolite AR-C124910XX after a single oral dose of ticagrelor. The fecal microbial compositions of individuals who exhibited distinct pharmacokinetic parameters were analyzed using 16S rRNA gene sequencing. Additionally, we conducted experiments involving the co-incubation of ticagrelor with fecal bacteria and a systematic exploration of the pharmacokinetics of ticagrelor in pseudo-germ-free (PGF) rats to illustrate the role of gut microbiota in ticagrelor metabolism, both in vitro and in vivo. Our findings revealed a three-fold difference in the bioavailability of ticagrelor among individuals. However, no difference was found in the composition of gut microbiota among individuals with different pharmacokinetic parameters. Quantitative analysis showed that gut microbiota cannot directly metabolize ticagrelor. Furthermore, there were no significant differences in AUC(0–48), AUC(0-∞), and Cmax between ticagrelor and AR-C124910XX in PGF rats compared to normal control, either by single intragastric or intravenous administration. In conclusion, these findings suggest that gut microbiota has no impact on the pharmacokinetics of ticagrelor.
SN - 1932-6203
ER -