A phase I safety and pharmacokinetic study of a recombinant amino terminal fragment of bactericidal/permeability-increasing protein in healthy male volunteers.
A phase I pharmacokinetic and safety clinical trial of rBPI23, a recombinant amino terminal fragment of bactericidal/permeability-increasing protein, was conducted in healthy male volunteers. rBPI23 was administered as a 5 or 30 min infusion at doses of .1 to 1 mg/kg. The pharmacokinetics of rBPI23 in human subjects were described by a bi-exponential disposition function with evidence of concentration-dependent kinetics. The alpha half-life increased significantly with increasing dose, from 4-5 min at .1 mg/kg to 7-8 min at 1 mg/kg. The beta half-life varied between 18 and 29 min regardless of dose and the clearance varied from 5 to 10 mL/min/kg. Very little, if any, of the administered rBPI23 was excreted intact in the urine. Electrocardiograms, ionized calcium concentration, prothrombin and partial prothrombin times, hematologic parameters, and blood chemistries remained normal. Furthermore, no antibody response to rBPI23 was observed in any of the subjects.
Bauer
R J
RJ
XOMA Corporation, Berkeley, California 94710, USA.
White
M L
ML
Wedel
N
N
Nelson
B J
BJ
Friedmann
N
N
Cohen
A
A
Hustinx
W N
WN
Kung
A H
AH
D000293:Adolescent; D000328:Adult; D001774:Blood Chemical Analysis; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008565:Membrane Proteins / Q000493:pharmacokinetics* / Q000494:pharmacology
D008565:Membrane Proteins; C025357:endotoxin binding proteins