Phase I evaluation of the safety and pharmacokinetics of a single-dose intravenous injection of a murine monoclonal antibody against Hantaan virus in healthy volunteers.

Anti-Hantaan virus monoclonal antibody (AHM) is a murine monoclonal antibody against Hantaan virus being developed for the treatment of hemorrhagic fever with renal syndrome. The purpose of the present study was to describe the tolerance and pharmacokinetics of an intravenously administered single ascending dose of AHM in Chinese healthy volunteers. Four cohorts of 22 healthy subjects received AHM at 2.5 to 20 mg, and the results indicated that AHM was well tolerated. We established a highly sensitive, rapid, and accurate immunoassay for the kinetic analysis of AHM in serum. Serial blood samples were obtained after intravenous administration for up to 17 days. A one-compartment model was determined to best describe the disposition of AHM. The maximal level in serum and the area under the serum concentration-time curve were proportional to the doses. The mean clearance, the half-life, and the volume of distribution were constant, irrespective of the dose. AHM was slowly cleared and had a half-life of approximately 110 h. These data support the use of a treatment regimen in which AHM is given only once intravenously.

RCT Entities:   Population Interventions Outcomes