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.
Bauer
R J
RJ
XOMA (US)LLC, Berkeley, California 94710, USA.
Wedel
N
N
Havrilla
N
N
White
M
M
Cohen
A
A
Carroll
S F
SF
D000293:Adolescent; D000328:Adult; D001419:Bacteria / Q000187:drug effects* / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects*; D004311:Double-Blind Method; D006801:Humans; D008565:Membrane Proteins / Q000097:blood / Q000235:genetics / Q000493:pharmacokinetics*; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012016:Reference Values; D013997:Time Factors
D008565:Membrane Proteins; D011994:Recombinant Proteins; C025357:endotoxin binding proteins