کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9954676 | 1554982 | 2018 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Pharmacokinetics of human recombinant C1-esterase inhibitor and development of anti-drug antibodies in healthy dogs
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کلمات کلیدی
no adverse effect levelCmaxImmune-mediated hemolytic anemiat½AUClasttmaxNOAELC1-INHPNHAUC - AUCanti-drug antibodies - آنتی بادی ضد داروtotal body clearance - ترخیص کامل بدنmaximum observed plasma concentration - حداکثر غلظت پلاسما مشاهده شدهIMHA - دفعpharmacokinetic - فارماکوکینتیکComplement - متممarea under the curve - منطقه تحت منحنیMAC - مکterminal half-life - نیمه عمر پایانیparoxysmal nocturnal hemoglobinuria - هموگلوبینوری شب ادراری پراکسیاسمیmembrane attack complex - پیچیده حمله غشاء
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم کشاورزی و بیولوژیک
علوم دامی و جانورشناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
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 500âIU 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 1440âmin post drug administration. Complete blood counts were conducted at baseline, 720 and 1440âmin. 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 0.21âIU/mL and that C1-INH concentration is significantly greater than baseline for 100âmin 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Veterinary Immunology and Immunopathology - Volume 203, September 2018, Pages 66-72
Journal: Veterinary Immunology and Immunopathology - Volume 203, September 2018, Pages 66-72
نویسندگان
Cheryl Wong, Daniela Hernandez Muguiro, Sidonie Lavergne, Erica Behling-Kelly, Robert Goggs,