title: Pharmacokinetics and pharmacodynamics of recombinant soluble thrombomodulin in disseminated intravascular coagulation patients with renal impairment.
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 severe renal impairment (creatinine clearance <30 mL/min) and 10 DIC patients without severe renal impairment (creatinine clearance ≥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.
authors.affiliation: Emergency and Critical Care Center, Hokkaido University Hospital. mineji@dream.com
authors.forename: Mineji
authors.initials: M
authors.lastname: Hayakawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Taeko
authors.initials: T
authors.lastname: Honma
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Mukai
authors.forename: Asumi
authors.initials: A
authors.lastname: Higashiyama
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sugano
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Kubota
authors.forename: Shinji
authors.initials: S
authors.lastname: Uegaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sawamura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Gando
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D004211:Disseminated Intravascular Coagulation / Q000150:complications / Q000378:metabolism*; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000150:complications* / Q000378:metabolism; D008297:Male; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology; D018180:Thrombomodulin / Q000378:metabolism* / Q000627:therapeutic use; D013925:Thromboplastin / Q000032:analysis
chemical_list: D000925:Anticoagulants; D011994:Recombinant Proteins; C546931:THBD protein, human; D018180:Thrombomodulin; D013925:Thromboplastin