NPT-IIb Inhibition Does Not Improve Hyperphosphatemia in CKD
| العنوان: | NPT-IIb Inhibition Does Not Improve Hyperphosphatemia in CKD |
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| المؤلفون: | Ronald A. Smulders, Tobias E. Larsson, Yuta Taniuchi, Chisato Kameoka, Tadao Akizawa, Satoshi Yoshida, Ikumi Nakajo |
| المصدر: | Kidney International Reports, Vol 3, Iss 1, Pp 73-80 (2018) Kidney International Reports |
| بيانات النشر: | Elsevier, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | medicine.medical_specialty, medicine.medical_treatment, Urinary system, 030232 urology & nephrology, 030204 cardiovascular system & hematology, lcsh:RC870-923, Gastroenterology, End stage renal disease, Excretion, 03 medical and health sciences, chemistry.chemical_compound, Hyperphosphatemia, 0302 clinical medicine, phase 1 trial, Pharmacokinetics, Clinical Research, Internal medicine, medicine, NPT-IIb inhibitor, hyperphosphatemia, end-stage renal disease, hemodialysis, business.industry, Phosphate, medicine.disease, lcsh:Diseases of the genitourinary system. Urology, Endocrinology, chemistry, Tolerability, Nephrology, Hemodialysis, business, pharmacokinetics |
| الوصف: | Introduction Serum phosphate levels are insufficiently controlled in many patients with end-stage renal disease (ESRD), and novel therapeutic strategies are needed. Blocking intestinal phosphate absorption mediated by sodium-dependent phosphate co-transporter type 2b (NPT-IIb) holds promise; thus, we evaluated the efficacy, safety, tolerability, and pharmacokinetics of the novel and specific small molecule NPT-IIb inhibitor ASP3325 for the first time in humans. Methods We conducted a randomized, double-blind, placebo-controlled, phase 1a single (n = 88) and multiple (n = 36) ascending dose study in healthy subjects, and a randomized, open-label, uncontrolled, phase 1b study in hyperphosphatemic ESRD patients on hemodialysis (single oral dose, n = 5; multiple oral doses, n = 17). Primary efficacy measures were urinary phosphate and fecal phosphorous excretion (healthy subjects) and serum phosphate level (ESRD patients). Results No time- or dose-dependent changes in urinary phosphate or fecal phosphorous excretion were observed following single/multiple ASP3325 doses for 7 days in healthy subjects. In ESRD patients, ASP3325 administered 3 times daily for 2 weeks before or after a meal did not reduce serum phosphate levels. ASP3325 was safe and well tolerated in both populations. Conclusion NPT-IIb inhibition with ASP3325 was not effective in reducing serum phosphate levels in ESRD patients. The relevance of NPT-IIb in humans and feasibility of oral NPT-IIb inhibitors for treatment of hyperphosphatemia in ESRD remain uncertain. |
| اللغة: | English |
| تدمد: | 2468-0249 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0aeec6f3ddb4d0f5844e3307eafe59dcTest http://www.sciencedirect.com/science/article/pii/S2468024917303455Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0aeec6f3ddb4d0f5844e3307eafe59dc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 24680249 |
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