caa a22 4500 477128157 CHVBK 20180405111656.0 cr unu---uuuuu 170330e19970201xx s 000 0 eng 10.1023/A:1012013113759 doi (NATIONALLICENCE)springer-10.1023/A:1012013113759 The Role of Liver and Kidney on the Pharmacokinetics of a Recombinant Amino Terminal Fragment of Bactericidal/Permeability-Increasing Protein in Rats [Elektronische Daten] [Robert Bauer, Kenneth Der, Nneka Ottah-Ihejeto, Jennifer Barrientos, Ada Kung] Purpose. The pharmacokinetics of rBPI23, a recombinant amino terminal fragment of bactericidal/permeability-increasing protein that binds to and neutralizes endotoxin, was investigated. Methods. rBPI23 was administered to rats at doses 0.01−10 mg/kg and plasma rBPI23 levels were measured by ELISA. rBPI23 was also administered to bilaterally nephrectomized rats. In addition, rBPI23 was administered intra-hepatically via the pyloric vein to determine the first-pass effect by the liver. rBPI23 concentrations were also simultaneously measured in the right atrium and aorta to determine the removal of rBPI23 by the lungs. Results. The concentration-time profile of rBPI23 was described by a 3-compartmental model with parallel first order and Michaelis-Menten (saturable) elimination. The clearance of rBPI23 was not altered by bilateral nephrectomy. Clearance of intra-hepatically administered rBPI23 was 4.5 fold lower than intra-femorally administered rBPI23. The concentration difference of rBPI23 between aortic and right atrial blood was no greater than 11%. Clearance of rBPI23 in rats could be reduced up to 10 fold by co-administration of heparin. Uptake by liver of intra-hepatically administered rBPI23 was prevented by co-administration of heparin. Conclusions. rBPI23 is not significantly cleared by the kidneys, and no more than 11% of the rBPI23 was removed by the lungs with each pass. The liver could remove 78% of the rBPI23 from the hepatic circulation. Studies with heparin suggest rBPI23 is cleared by binding to heparan sulfate sites in the liver. Plenum Publishing Corporation, 1997 bactericidal/permeability-increasing protein nationallicence pharmacokinetics nationallicence liver nationallicence kidney nationallicence heparin nationallicence Bauer Robert aut Der Kenneth aut Ottah-Ihejeto Nneka aut Barrientos Jennifer aut Kung Ada aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/2(1997-02-01), 224-229 0724-8741 14:2<224 1997 14 11095 https://doi.org/10.1023/A:1012013113759 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012013113759 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Bauer Robert aut NATIONALLICENCE 700 1- Der Kenneth aut NATIONALLICENCE 700 1- Ottah-Ihejeto Nneka aut NATIONALLICENCE 700 1- Barrientos Jennifer aut NATIONALLICENCE 700 1- Kung Ada aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/2(1997-02-01), 224-229 0724-8741 14:2<224 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer