Pharmacokinetics of a recombinant modified amino terminal fragment of bactericidal/permeability-increasing protein (rBPI(21)) in healthy volunteers

Phase 1 pharmacokinetic and safety studies were conducted in healthy volunt eers with rBPI(21), a recombinant protein derived from the amino terminal d omain of human bactericidal/permeability-increasing protein. rBPI(21) was a dministered 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 rBPI(21) decreased with increasing dose from 8.4 mL/min/k g at 0.25 mg/kg to 3.3 mL/min/kg at 4 mg/kg. For rBPI(21) infused over 24 t o 48 hours the clearance was 10 to 11 mL/min/kg. The concentration-time pro file of rBPI(21) was well described by a three-compartmental model with par allel first-order and Michaelis-Menten (saturable) elimination. This model for the clearance of rBPI(21) has been useful in estimating starting doses for therapeutic clinical trials. (C) 1999 the American College of Clinical Pharmacology.