Dabigatran Acylglucuronide, the Major Metabolite of Dabigatran, Shows a Weaker Anticoagulant Effect than Dabigatran
Dabigatran (DAB) is an orally administered thrombin inhibitor. Both DAB and its main metabolite dabigatran acylglucuronide (DABG) have established anticoagulant effects. Here, we aimed to compare the relative anticoagulant effects of DABG and DAB in humans. Anticoagulant effects of DAB and DABG were...
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2022-01-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/2/257 |
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| author | Jong-Min Kim Jihyeon Noh Jin-Woo Park Hyewon Chung Kyoung-Ah Kim Seung Bin Park Jun-Seok Lee Ji-Young Park |
| author_facet | Jong-Min Kim Jihyeon Noh Jin-Woo Park Hyewon Chung Kyoung-Ah Kim Seung Bin Park Jun-Seok Lee Ji-Young Park |
| author_sort | Jong-Min Kim |
| collection | DOAJ |
| description | Dabigatran (DAB) is an orally administered thrombin inhibitor. Both DAB and its main metabolite dabigatran acylglucuronide (DABG) have established anticoagulant effects. Here, we aimed to compare the relative anticoagulant effects of DABG and DAB in humans. Anticoagulant effects of DAB and DABG were measured in vitro using a thrombin generation assay. Additionally, their effects on other coagulation assays including PT, aPTT, TT, and fibrinogen were compared. Both DAB and DABG showed inhibitory effects on thrombin generation in a dose-dependent manner, but DABG exhibited a weaker inhibitory effect than that of DAB. The IC<sub>50</sub> values of DAB and DABG on thrombin generation AUC were 134.1 ng/mL and 281.9 ng/mL, respectively. DABG also exhibited weaker anticoagulant effects than DAB on PT, aPTT, and TT. The results of the present study indicate that the anticoagulant effect of DABG, a main active DAB metabolite, is weaker than that of DAB. |
| first_indexed | 2024-03-09T21:15:28Z |
| format | Article |
| id | doaj.art-f39bc2e2824848099f85e3e3c71ecf98 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T21:15:28Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-f39bc2e2824848099f85e3e3c71ecf982023-11-23T21:36:15ZengMDPI AGPharmaceutics1999-49232022-01-0114225710.3390/pharmaceutics14020257Dabigatran Acylglucuronide, the Major Metabolite of Dabigatran, Shows a Weaker Anticoagulant Effect than DabigatranJong-Min Kim0Jihyeon Noh1Jin-Woo Park2Hyewon Chung3Kyoung-Ah Kim4Seung Bin Park5Jun-Seok Lee6Ji-Young Park7Department of Clinical Pharmacology and Toxicology, Korea University College of Medicine, Korea University Anam Hospital, Seoul 02841, KoreaDepartment of Clinical Pharmacology and Toxicology, Korea University College of Medicine, Korea University Anam Hospital, Seoul 02841, KoreaDepartment of Neurology, Korea University College of Medicine, Korea University Anam Hospital, Seoul 02841, KoreaDepartment of Clinical Pharmacology and Toxicology, Korea University Guro Hospital, Seoul 08308, KoreaDepartment of Clinical Pharmacology and Toxicology, Korea University College of Medicine, Korea University Anam Hospital, Seoul 02841, KoreaDepartment of Pharmacology, Korea University College of Medicine, Korea University, Seoul 02841, KoreaDepartment of Pharmacology, Korea University College of Medicine, Korea University, Seoul 02841, KoreaDepartment of Clinical Pharmacology and Toxicology, Korea University College of Medicine, Korea University Anam Hospital, Seoul 02841, KoreaDabigatran (DAB) is an orally administered thrombin inhibitor. Both DAB and its main metabolite dabigatran acylglucuronide (DABG) have established anticoagulant effects. Here, we aimed to compare the relative anticoagulant effects of DABG and DAB in humans. Anticoagulant effects of DAB and DABG were measured in vitro using a thrombin generation assay. Additionally, their effects on other coagulation assays including PT, aPTT, TT, and fibrinogen were compared. Both DAB and DABG showed inhibitory effects on thrombin generation in a dose-dependent manner, but DABG exhibited a weaker inhibitory effect than that of DAB. The IC<sub>50</sub> values of DAB and DABG on thrombin generation AUC were 134.1 ng/mL and 281.9 ng/mL, respectively. DABG also exhibited weaker anticoagulant effects than DAB on PT, aPTT, and TT. The results of the present study indicate that the anticoagulant effect of DABG, a main active DAB metabolite, is weaker than that of DAB.https://www.mdpi.com/1999-4923/14/2/257dabigatrandabigatran acylglucuronidethrombin generationanticoagulation |
| spellingShingle | Jong-Min Kim Jihyeon Noh Jin-Woo Park Hyewon Chung Kyoung-Ah Kim Seung Bin Park Jun-Seok Lee Ji-Young Park Dabigatran Acylglucuronide, the Major Metabolite of Dabigatran, Shows a Weaker Anticoagulant Effect than Dabigatran Pharmaceutics dabigatran dabigatran acylglucuronide thrombin generation anticoagulation |
| title | Dabigatran Acylglucuronide, the Major Metabolite of Dabigatran, Shows a Weaker Anticoagulant Effect than Dabigatran |
| title_full | Dabigatran Acylglucuronide, the Major Metabolite of Dabigatran, Shows a Weaker Anticoagulant Effect than Dabigatran |
| title_fullStr | Dabigatran Acylglucuronide, the Major Metabolite of Dabigatran, Shows a Weaker Anticoagulant Effect than Dabigatran |
| title_full_unstemmed | Dabigatran Acylglucuronide, the Major Metabolite of Dabigatran, Shows a Weaker Anticoagulant Effect than Dabigatran |
| title_short | Dabigatran Acylglucuronide, the Major Metabolite of Dabigatran, Shows a Weaker Anticoagulant Effect than Dabigatran |
| title_sort | dabigatran acylglucuronide the major metabolite of dabigatran shows a weaker anticoagulant effect than dabigatran |
| topic | dabigatran dabigatran acylglucuronide thrombin generation anticoagulation |
| url | https://www.mdpi.com/1999-4923/14/2/257 |
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