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Pharmacokinetics of human recombinant C1-esterase inhibitor and development of anti-drug antibodies in healthy dogs.
Vet Immunol Immunopathol 2018; 203:66-72VI

Abstract

Complement-mediated intravascular hemolysis occurs in canine immune-mediated hemolytic anemia (IMHA). Complement inhibitors such as recombinant C1 esterase inhibitor (rC1-INH) might prevent this process and alter the disease course. This study aimed to characterize the pharmacokinetics of a single 500 IU IV dose of rC1-INH in 8 healthy beagle dogs, evaluate the dogs for any adverse effects of drug administration, and determine whether rC1-INH administration induces anti-drug antibody formation. Serum rC1-INH concentrations were measured using a commercial functional ELISA at baseline and at 10, 20, 40, 60, 80, 100, 120, 240, 360, 480, 600, 720, 960, and 1440 min post drug administration. Complete blood counts were conducted at baseline, 720 and 1440 min. Western blot analysis, using rC1-INH as the target antigen was used to detect anti-drug antibodies in 14-day serum samples. No adverse clinical reactions were noted following rC1-INH administration. Pharmacokinetic modelling suggested that the peak C1-INH concentration achieved is 0.21 IU/mL and that C1-INH concentration is significantly greater than baseline for 100 min following injection. A robust antibody response was detected which suggests that rC1-INH should not be re-administered after an initial course. Clinical trials of rC1-INH in dogs with intravascular IMHA are now warranted.

Authors+Show Affiliations

Department of Population Medicine, Cornell University College of Veterinary Medicine, Ithaca, NY, 14853, United States.Department of Population Medicine, Cornell University College of Veterinary Medicine, Ithaca, NY, 14853, United States.Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Illinois, Urbana, IL, 61802, United States.Department of Population Medicine, Cornell University College of Veterinary Medicine, Ithaca, NY, 14853, United States.Department of Clinical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY, 14853, United States. Electronic address: r.goggs@cornell.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30243377

Citation

Wong, Cheryl, et al. "Pharmacokinetics of Human Recombinant C1-esterase Inhibitor and Development of Anti-drug Antibodies in Healthy Dogs." Veterinary Immunology and Immunopathology, vol. 203, 2018, pp. 66-72.
Wong C, Muguiro DH, Lavergne S, et al. Pharmacokinetics of human recombinant C1-esterase inhibitor and development of anti-drug antibodies in healthy dogs. Vet Immunol Immunopathol. 2018;203:66-72.
Wong, C., Muguiro, D. H., Lavergne, S., Behling-Kelly, E., & Goggs, R. (2018). Pharmacokinetics of human recombinant C1-esterase inhibitor and development of anti-drug antibodies in healthy dogs. Veterinary Immunology and Immunopathology, 203, pp. 66-72. doi:10.1016/j.vetimm.2018.08.006.
Wong C, et al. Pharmacokinetics of Human Recombinant C1-esterase Inhibitor and Development of Anti-drug Antibodies in Healthy Dogs. Vet Immunol Immunopathol. 2018;203:66-72. PubMed PMID: 30243377.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetics of human recombinant C1-esterase inhibitor and development of anti-drug antibodies in healthy dogs. AU - Wong,Cheryl, AU - Muguiro,Daniela Hernandez, AU - Lavergne,Sidonie, AU - Behling-Kelly,Erica, AU - Goggs,Robert, Y1 - 2018/08/23/ PY - 2018/05/24/received PY - 2018/08/02/revised PY - 2018/08/15/accepted PY - 2018/9/24/entrez PY - 2018/9/24/pubmed PY - 2018/11/9/medline KW - Anti-drug antibodies KW - C1-INH KW - C3 KW - Complement KW - IMHA KW - Ruconest SP - 66 EP - 72 JF - Veterinary immunology and immunopathology JO - Vet. Immunol. Immunopathol. VL - 203 N2 - Complement-mediated intravascular hemolysis occurs in canine immune-mediated hemolytic anemia (IMHA). Complement inhibitors such as recombinant C1 esterase inhibitor (rC1-INH) might prevent this process and alter the disease course. This study aimed to characterize the pharmacokinetics of a single 500 IU IV dose of rC1-INH in 8 healthy beagle dogs, evaluate the dogs for any adverse effects of drug administration, and determine whether rC1-INH administration induces anti-drug antibody formation. Serum rC1-INH concentrations were measured using a commercial functional ELISA at baseline and at 10, 20, 40, 60, 80, 100, 120, 240, 360, 480, 600, 720, 960, and 1440 min post drug administration. Complete blood counts were conducted at baseline, 720 and 1440 min. Western blot analysis, using rC1-INH as the target antigen was used to detect anti-drug antibodies in 14-day serum samples. No adverse clinical reactions were noted following rC1-INH administration. Pharmacokinetic modelling suggested that the peak C1-INH concentration achieved is 0.21 IU/mL and that C1-INH concentration is significantly greater than baseline for 100 min following injection. A robust antibody response was detected which suggests that rC1-INH should not be re-administered after an initial course. Clinical trials of rC1-INH in dogs with intravascular IMHA are now warranted. SN - 1873-2534 UR - https://www.unboundmedicine.com/medline/citation/30243377/Pharmacokinetics_of_human_recombinant_C1-esterase_inhibitor_and_development_of_anti-drug_antibodies_in_healthy_dogs L2 - https://linkinghub.elsevier.com/retrieve/pii/S0165-2427(18)30223-X DB - PRIME DP - Unbound Medicine ER -