Redistribution and enhanced urinary excretion of 2,2',4,4',5,5'-hexachlorobiphenyl (HCB) in rats using HCB-specific IgG and Fab fragments.
Drug-specific antibody fragments can enhance the elimination of some drugs by redistributing drug from tissues into serum and allowing renal excretion of the drug-antibody complex. This approach could potentially be used to enhance the elimination of compounds such as polychlorinated biphenyls that have very long elimination half-lives. As a first step in testing this hypothesis, the effects of 2,2',4,4',5,5'-hexachlorobiphenyl (HCB)-specific antibodies and their corresponding Fab fragments on HCB disposition were studied in rats. Antibodies to HCB were produced in chickens, and the corresponding Fab fragments were produced by digestion with papain. To study antibody effects on HCB distribution, [14C]HCB (0.1 mg) was administered i.v. to rats. Two weeks later, after distribution to tissues was complete, anti-HCB IgG or control IgG was administered i.v. The serum radiolabel concentration 2 hr after IgG administration increased 185 +/- 64% in animals treated with specific antibody vs 51 +/- 19% in control animals (P < 0.001). The increase in serum radiolabel concentration was apparent within 30 min and maximal at 2 hr. To study effects on HCB excretion, anti-HCB or control Fab fragment was administered 2 weeks after [14C]HCB. Urinary HCB excretion over the next 24 hr, measured by gas chromatography, was 10-fold greater in the group treated with anti-HCB Fab (P < 0.01). These data demonstrate that anti-HCB IgG can redistribute HCB rapidly from tissues into serum and that anti-HCB Fab can enhance urinary HCB excretion. While the magnitude of these changes was small, the data suggest that increasing HCB excretion using drug-specific antibody fragments is feasible, and can serve as a model for enhancing the excretion of compounds that have very long elimination half-lives.
Keyler
D E
DE
Department of Medicine, Hennepin County Medical Center, University of Minnesota Medical School, Minneapolis.
Goon
D J
DJ
Shelver
W L
WL
Ross
C A
CA
Nagasawa
H T
HT
St Peter
J V
JV
Pentel
P R
PR
D000818:Animals; D000936:Antigen-Antibody Complex / Q000652:urine; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000494:pharmacology; D007128:Immunoglobulin Fragments / Q000276:immunology / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D011078:Polychlorinated Biphenyls / Q000276:immunology* / Q000493:pharmacokinetics* / Q000652:urine; D051381:Rats
D000936:Antigen-Antibody Complex; D007140:Immunoglobulin Fab Fragments; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D011078:Polychlorinated Biphenyls; C014024:2,4,5,2',4',5'-hexachlorobiphenyl