Evaluation of Pharmacokinetic Drug–Drug Interactions: A Review of the Mechanisms, In Vitro and In Silico Approaches
Pharmacokinetic drug–drug interactions (DDIs) occur when a drug alters the absorption, transport, distribution, metabolism or excretion of a co-administered agent. The occurrence of pharmacokinetic DDIs may result in the increase or the decrease of drug concentrations, which can significantly affect...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/11/2/75 |
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| author | Yaru Peng Zeneng Cheng Feifan Xie |
| author_facet | Yaru Peng Zeneng Cheng Feifan Xie |
| author_sort | Yaru Peng |
| collection | DOAJ |
| description | Pharmacokinetic drug–drug interactions (DDIs) occur when a drug alters the absorption, transport, distribution, metabolism or excretion of a co-administered agent. The occurrence of pharmacokinetic DDIs may result in the increase or the decrease of drug concentrations, which can significantly affect the drug efficacy and safety in patients. Enzyme-mediated DDIs are of primary concern, while the transporter-mediated DDIs are less understood but also important. In this review, we presented an overview of the different mechanisms leading to DDIs, the in vitro experimental tools for capturing the factors affecting DDIs, and in silico methods for quantitative predictions of DDIs. We also emphasized the power and strategy of physiologically based pharmacokinetic (PBPK) models for the assessment of DDIs, which can integrate relevant in vitro data to simulate potential drug interaction in vivo. Lastly, we pointed out the future directions and challenges for the evaluation of pharmacokinetic DDIs. |
| first_indexed | 2024-03-09T03:30:46Z |
| format | Article |
| id | doaj.art-b1397b3bb7ec48b29ad652d91ea69481 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-09T03:30:46Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-b1397b3bb7ec48b29ad652d91ea694812023-12-03T14:55:45ZengMDPI AGMetabolites2218-19892021-01-011127510.3390/metabo11020075Evaluation of Pharmacokinetic Drug–Drug Interactions: A Review of the Mechanisms, In Vitro and In Silico ApproachesYaru Peng0Zeneng Cheng1Feifan Xie2Division of Biopharmaceutics and Pharmacokinetics, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, ChinaDivision of Biopharmaceutics and Pharmacokinetics, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, ChinaDivision of Biopharmaceutics and Pharmacokinetics, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, ChinaPharmacokinetic drug–drug interactions (DDIs) occur when a drug alters the absorption, transport, distribution, metabolism or excretion of a co-administered agent. The occurrence of pharmacokinetic DDIs may result in the increase or the decrease of drug concentrations, which can significantly affect the drug efficacy and safety in patients. Enzyme-mediated DDIs are of primary concern, while the transporter-mediated DDIs are less understood but also important. In this review, we presented an overview of the different mechanisms leading to DDIs, the in vitro experimental tools for capturing the factors affecting DDIs, and in silico methods for quantitative predictions of DDIs. We also emphasized the power and strategy of physiologically based pharmacokinetic (PBPK) models for the assessment of DDIs, which can integrate relevant in vitro data to simulate potential drug interaction in vivo. Lastly, we pointed out the future directions and challenges for the evaluation of pharmacokinetic DDIs.https://www.mdpi.com/2218-1989/11/2/75drug–drug interactionspharmacokineticsphysiologically based pharmacokinetic modelcytochrome P450transporter |
| spellingShingle | Yaru Peng Zeneng Cheng Feifan Xie Evaluation of Pharmacokinetic Drug–Drug Interactions: A Review of the Mechanisms, In Vitro and In Silico Approaches Metabolites drug–drug interactions pharmacokinetics physiologically based pharmacokinetic model cytochrome P450 transporter |
| title | Evaluation of Pharmacokinetic Drug–Drug Interactions: A Review of the Mechanisms, In Vitro and In Silico Approaches |
| title_full | Evaluation of Pharmacokinetic Drug–Drug Interactions: A Review of the Mechanisms, In Vitro and In Silico Approaches |
| title_fullStr | Evaluation of Pharmacokinetic Drug–Drug Interactions: A Review of the Mechanisms, In Vitro and In Silico Approaches |
| title_full_unstemmed | Evaluation of Pharmacokinetic Drug–Drug Interactions: A Review of the Mechanisms, In Vitro and In Silico Approaches |
| title_short | Evaluation of Pharmacokinetic Drug–Drug Interactions: A Review of the Mechanisms, In Vitro and In Silico Approaches |
| title_sort | evaluation of pharmacokinetic drug drug interactions a review of the mechanisms in vitro and in silico approaches |
| topic | drug–drug interactions pharmacokinetics physiologically based pharmacokinetic model cytochrome P450 transporter |
| url | https://www.mdpi.com/2218-1989/11/2/75 |
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