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Pharmacokinetics of a Recombinant Modified Amino Terminal Fragment of Bactericidal/Permeability‐Increasing Protein (rBPI 21 ) in Healthy Volunteers
Author(s) -
Bauer Robert J.,
Wedel Nancy,
Havrilla Nancy,
White Mark,
Cohen Albert,
Carroll Stephen F.
Publication year - 1999
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/009127009903901109
Subject(s) - pharmacokinetics , recombinant dna , amino terminal , terminal (telecommunication) , chemistry , pharmacology , medicine , peptide sequence , biochemistry , computer science , gene , telecommunications
Phase I pharmacokinetic and safety studies were conducted in healthy volunteers with rBPI 21 , a recombinant protein derived from the amino terminal domain of human bactericidal/permeability‐increasing protein. rBPI 21 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 rBPI 21 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 rBPI 21 infused over 24 to 48 hours the clearance was 10 to 11 mL/min/kg. The concentration‐time profile of rBPI 21 was well described by a three‐compartmental model with parallel 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 .