Model-based analysis of covariate effects on population pharmacokinetics of thrombomodulin alfa in patients with disseminated intravascular coagulation and normal subjects

Kazuhisa Tsuruta, Yoshinobu Yamada, Masashi Serada, Yusuke Tanigawara

研究成果: Article

25 引用 (Scopus)

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Thrombomodulin alfa is the recombinant extracellular domain of human thrombomodulin, which shows anticoagulation activity. To elucidate the pharmacokinetics of thrombomodulin alfa in patients with disseminated intravascular coagulation (DIC), population pharmacokinetic (PPK) analysis was performed using plasma concentration data obtained in phase 1 (20 patients, 348 time points) and phase 2 (116 patients, 305 time points) clinical trials. The actual and predicted plasma concentrations of thrombomodulin alfa based on the final PPK model showed a good linear correlation (R = 0.9504), and the pharmacokinetics of thrombomodulin alfa in DIC patients were affected by body weight, age, renal dysfunction, and hematocrit value. The distribution volume and clearance (CL) were proportional to body weight and were significantly increased in patients with lower hematocrit value (male <40%, female <35%). Furthermore, CL was decreased in patients with renal dysfunction and in elderly patients. Based on these results, the standard dose of thrombomodulin alfa is adjusted according to body weight. However, further dose adjustment is not needed based on age and hematocrit value, since these factors did not cause the large changes in plasma concentration that can affect the efficacy or safety.

元の言語English
ページ(範囲)1276-1285
ページ数10
ジャーナルJournal of Clinical Pharmacology
51
発行部数9
DOI
出版物ステータスPublished - 2011 9 1

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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