| Title: | Pharmacokinetics and pharmacodynamics of recombinant soluble thrombomodulin in disseminated intravascular coagulation patients with renal impairment |
| Authors: | Hayakawa, Mineji Browse this author →KAKEN DB |
| Yamamoto, Hiroshi Browse this author |
| Honma, Taeko Browse this author |
| Mukai, Nobutaka Browse this author |
| Higashiyama, Asumi Browse this author |
| Sugano, Masahiro Browse this author |
| Kubota, Nobuhiko Browse this author |
| Uegaki, Shinji Browse this author |
| Sawamura, Atsushi Browse this author →KAKEN DB |
| Gando, Satoshi Browse this author →KAKEN DB |
| Keywords: | Disseminated intravascular coagulation |
| thrombomodulin |
| renal dysfunction |
| prothrombinase activity |
| protein C |
| clearance |
| Issue Date: | Jun-2012 |
| Publisher: | Lippincott Williams & Wilkins |
| Journal Title: | Shock |
| Volume: | 37 |
| Issue: | 6 |
| Start Page: | 569 |
| End Page: | 573 |
| Publisher DOI: | 10.1097/SHK.0b013e318252bc82 |
| PMID: | 22552020 |
| Abstract: | Recombinant human soluble thrombomodulin (TM-α) was recently developed as an anticoagulant for patients with disseminated intravascular coagulation (DIC). However, the pharmacokinetics and pharmacodynamics of TM-α in DIC patients with severe renal impairment have not yet been elucidated. We investigated the pharmacokinetics and pharmacodynamics of TM-α in DIC patients with severe renal impairment. Eleven DIC patients with the severe renal impairment (creatinine clearance (CLcr) <30 ml/min) and 10 DIC patients without severe renal impairment (CLcr ≥ 30 ml/min) were included in this study. In all patients, a dose of 380 U/kg of TM-α was administered during a 30 min infusion. Blood samples were taken before the start of the first TM-α administration, and at 0.5, 2, 4, 8, and 24 h after the start of administration. Although the clearance of TM-α in the patients with renal impairment was 80% of that in the patients without renal impairment, none of the pharmacokinetic values were significantly different between the groups. In the pharmacokinetic simulation, however, the trough levels of TM-α increased gradually in the patients with renal impairment when the same dose of TM-α was repeatedly administered. After the administration of TM-α, the prothrombinase activities in the patients in both groups were sufficiently inhibited during the observation period. Although the pharmacokinetic values in DIC patients with severe renal impairment were only slightly different from those in DIC patients without severe renal impairment, we need to pay attention to the elevation of the trough levels of TM-α when the same dose of TM-α is repeatedly administered. |
| Rights: | This is a non-final version of an article published in final form in Shock, June 2012, 37(6), p 569-573 |
| Relation: | http://journals.lww.com/shockjournal/pages/default.aspx |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/52797 |
| Appears in Collections: | 北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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