薬理と治療

Abstract

Background Monteplase（Cleactor_）, a recombinant tissue plasminogen activator has beenused for the treatment of acute myocardial infarction. Recently, monteplase was authorized asa thrombolytic agent of acute pulmonary thromboembolism（APTE）. The pharmacokinetics（PK）of low dose monteplase was examined in healthy subjects, but not in patients withAPTE at approved doses.Objectives We investigated PK and pharmacodynamics（PD）of intravenous administrationof monteplase in patients with APTE at the approved dose（13750〜27500 IU/kg). Methods Five patients were enrolled at 2 institutions from May 2007 to April 2008. In all cases, we measured plasma antigen levels and activity levels for PK assessments and coagu- lating and fibrinolytic parameters for PD. Results According to plasma monteplase antigen levels and activity levels by model inde- pendent analysis, t1/2 was 1.23-7.00 hr and 33.0-40.2 min, respectively, and CLtot was 0.46- 0.94 mL/min/kg and 1.40-2.60 mL/min/kg, respectively. These results were similar to those of compartment model analysis. By the compartment model analysis, the PK parameters including tl/2 and CL were similar between APTE patients and healthy subjects. The changes in coagulating and fibrinolytic parameters post-dose were also similar in both groups. The changes in coagulating and fibrinolytic parameters were correlated with the change in antigen and activity levels in plasma. Conclusions The PK of intravenous administration of monteplase between APTE patients and healthy subjects was not noticeably different. The PD was also correlated with the changes in monteplase antigen and activity level. It was suggested that the changes in above parameters well corresponded to pharmacological actions of monteplase in patients with APTE.(Jpn Pharmacol Ther 2009;37:941-51) KEY WORDS Monteplase, Tissue-plasminogen activator, Pharmacokinetics, Pharmacody- namics, Acute pulmonary thromboembolism