Inter-individual variability in atrasentan exposure partly explains variability in kidney protection and fluid retention responses
| العنوان: | Inter-individual variability in atrasentan exposure partly explains variability in kidney protection and fluid retention responses |
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| المؤلفون: | John J.V. McMurray, Jasper Stevens, Sheldon W. Tobe, Hans-Henrik Parving, George Bakris, Fan Fan Hou, Vlado Perkovic, Ricardo Correa-Rotter, Hiddo J.L. Heerspink, Dalane W. Kitzman, Donald E. Kohan, Hirofumi Makino, Dick de Zeeuw, Jeroen V. Koomen |
| المساهمون: | Groningen Kidney Center (GKC), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET) |
| المصدر: | Diabetes, Obesity & Metabolism Diabetes obesity & metabolism, 561-568. Wiley ISSUE=2;STARTPAGE=561;ENDPAGE=568;ISSN=1462-8902;TITLE=Diabetes obesity & metabolism |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | medicine.medical_specialty, ALBUMINURIA, medicine.drug_class, Endocrinology, Diabetes and Metabolism, Population, Urology, Renal function, 030209 endocrinology & metabolism, atrasentan, diabetic kidney disease, endothelin receptor antagonist, pharmacodynamics, randomized controlled trial, 030204 cardiovascular system & hematology, Kidney, endothelin receptor antagonist, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Double-Blind Method, ENDOTHELIN, Internal Medicine, Natriuretic peptide, pharmacodynamics, Medicine, Humans, Diabetic Nephropathies, education, education.field_of_study, business.industry, atrasentan, Atrasentan, Original Articles, medicine.disease, Confidence interval, diabetic kidney disease, Diabetes Mellitus, Type 2, Pharmacodynamics, randomized controlled trial, Albuminuria, Original Article, medicine.symptom, business, Kidney disease, medicine.drug, Glomerular Filtration Rate |
| الوصف: | Aim: \ud To evaluate whether atrasentan plasma exposure explains between-patient variability in urinary albumin-to-creatinine ratio (UACR) response, a surrogate for kidney protection, and B-type natriuretic peptide (BNP) response, a surrogate for fluid expansion.\ud \ud Methods: \ud Type 2 diabetic patients with chronic kidney disease (n = 4775) received 0.75 mg atrasentan for 6 weeks in the active run-in period. Individual area under the concentration-time-curve (AUC) was estimated using a population pharmacokinetic model. The association between atrasentan AUC, other clinical characteristics, and UACR and BNP response, was estimated using linear regression.\ud \ud Results: \ud The median atrasentan AUC was 43.8 ng.h/mL with a large variation among patients (2.5th-97.5th percentiles [P]: 12.6 to 197.5 ng.h/mL). Median UACR change at the end of enrichment was −36.0% and median BNP change was 8.7%, which also varied among patients (UACR, 2.5th-97.5th P: −76.2% to 44.5%; BNP, 2.5th-97.5th P: −71.5% to 300.0%). In the multivariable analysis, higher atrasentan AUC was associated with greater UACR reduction (4.88% per doubling in ng.h/mL [95% confidence interval {CI}: 6.21% to 3.52%], P |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1462-8902 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::df22451d080c60bbcac114528f8a27e2Test https://research.rug.nl/en/publications/bf303280-19b5-4809-bd80-db4c520b0c12Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....df22451d080c60bbcac114528f8a27e2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14628902 |
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