Development of a two-site immunoassay of recombinant urate oxidase (SR 29142) and its use for determination of pharmacokinetic parameters in rats and baboons.
Two monoclonal antibodies (Mabs), 12C7 and 11G11, both directed against recombinant urate oxidase (SR 29142), were selected for their epitope specificity to develop a two-site immunoassay of urate oxidase in plasma. A quantitative recovery of urate oxidase in plasma was obtained at all the concentrations tested, and the limit of quantification was found to be 0.5 ng/mL. Intra-and interassay coefficients of variation ranged from 1.2 to 6.7% and from 3.5 to 10.8%, respectively. The specificity of the two antibodies was studied in Western-blot experiments. This assay was used successfully to determine urate oxidase pharmacokinetic parameters after intravenous injection in rats and baboons. In these two species, urate oxidase pharmacokinetics was characterized by a low clearance and a low volume of distribution without gender difference.
Dussossoy
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Sanofi Recherche, Montpellier, France.
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Pastor
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Boulenc
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D005260:Female; D007118:Immunoassay; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010215:Papio; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014503:Urate Oxidase / Q000032:analysis / Q000276:immunology / Q000493:pharmacokinetics*
D000911:Antibodies, Monoclonal; D014503:Urate Oxidase