Pharmacokinetics of a recombinant modified amino terminal fragment of bactericidal/permeability-increasing protein (rBPI21) in healthy volunteers

Phase I pharmacokinetic and safety studies were conducted in healthy volunteers with rBPI21, a recombinant protein derived from the amino terminal domain of human bactericidal/permeability-increasing protein. rBPI21 was administered as a 30-minute infusion at doses of 0.25 to 4 mg/kg or as a 24- to 48-hour infusion at doses of 2 to 8 mg/kg. For the 30-minute infusions, the clearance of rBPI21 decreased with increasing dose from 8.4 mL/min/kg at 0.25 mg/kg to 3.3 mL/min/kg at 4 mg/kg. For rBPI21 infused over 24 to 48 hours the clearance was 10 to 11 mL/min/kg. The concentration-time profile of rBPI21 was well described by a three-compartmental model with parallel first-order and Michaelis-Menten (saturable) elimination. This model for the clearance of rBPI21 has been useful in estimating starting doses for therapeutic clinical trials.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				S. Alexander, J. Bramson, R. Foley, and Z. Xing Protection from endotoxemia by adenoviral-mediated gene transfer of human bactericidal/permeability-increasing protein Blood, January 1, 2004; 103(1): 93 - 99. [Abstract] [Full Text] [PDF]