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Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Medicine / Faculty of Medicine >
Peer-reviewed Journal Articles, etc >
Pharmacokinetics of recombinant human soluble thrombomodulin in disseminated intravascular coagulation patients with acute renal dysfunction
This item is licensed under:Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
| Title: | Pharmacokinetics of recombinant human soluble thrombomodulin in disseminated intravascular coagulation patients with acute renal dysfunction |
| Authors: | Hayakawa, Mineji Browse this author →KAKEN DB | | Kushimoto, Shigeki Browse this author →KAKEN DB | | Watanabe, Eizo Browse this author | | Goto, Koji Browse this author | | Suzuki, Yasushi Browse this author | | Kotani, Toru Browse this author | | Kiguchi, Takeyuki Browse this author | | Yatabe, Tomoaki Browse this author | | Tagawa, Jun Browse this author | | Komatsu, Fumiyo Browse this author | | Gando, Satoshi Browse this author →KAKEN DB |
| Keywords: | Plasma concentration | | disseminated intravascular coagulation | | pharmacokinetics | | renal dysfunction | | sepsis |
| Issue Date: | 2017 |
| Publisher: | Schattauer GmbH |
| Journal Title: | Thrombosis and haemostasis |
| Volume: | 117 |
| Issue: | 5 |
| Start Page: | 851 |
| End Page: | 859 |
| Publisher DOI: | 10.1160/TH16-07-0547 |
| Abstract: | Recombinant human soluble thrombomodulin (ART-123) is a novel anticoagulant for patients with disseminated intravascular coagulation (DIC). It is widely used in clinical settings throughout Japan. Furthermore, a global Phase 3 study is currently being conducted. In healthy subjects, ART-123 is excreted mainly via the kidneys. Therefore, ART-123 dose decrease was recommended in DIC patients with severe renal dysfunction. However, the pharmacokinetics of ART-123 in DIC patients with severe acute renal dysfunction has not been elucidated. In an open-label, multicentre, prospective, clinical pharmacological study, we investigated the pharmacokinetics and safety of ART-123 upon repeated administration to DIC patients. ART-123 was administered to patients at a dose of 130 or 380 U/kg/day for six consecutive days. Plasma concentrations of ART-123 were measured at 21 time points until eight days after the final administration. Urinary ex-cretion rates during the first 24 hours (h) were calculated. Patient renal functions were evaluated by measuring 24-h creatinine clearance (Ccr). Forty-three patients were enrolled in the present study. The urinary excretion rates of ART-123 correlated closely with 24-h Ccr. Total body clearance of ART-123 was also weakly related with 24-h Ccr. However, the plasma concentrations of ART-123 were not considerably different among patients with different renal function. Two patients had subcutaneous haemorrhage as an adverse event related to ART-123. In conclusion, plasma concentrations of ART-123 may not be different among patients with different renal functions. ART-123 was well tolerated in these patients. |
| Rights: | https://creativecommons.org/licenses/by-nc-nd/4.0 |
| Type: | article |
| URI: | http://hdl.handle.net/2115/66559 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 早川 峰司
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