Erythropoietin alters the pharmacokinetics of organic anions mainly eliminated by the kidney in rats
Autor: | María Herminia Hazelhoff, María Julia Severin, Adriana M. Torres, Anabel Brandoni, María E. Mamprin, Romina Paula Bulacio |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Anions Male Organic anion transporter 1 Physiology medicine.medical_treatment Pharmacology Kidney 030226 pharmacology & pharmacy 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Physiology (medical) polycyclic compounds medicine Animals Rats Wistar Erythropoietin biology Chemistry General Medicine Rats Haematopoiesis 030104 developmental biology Cytokine medicine.anatomical_structure biology.protein Organic anion medicine.drug |
Zdroj: | Canadian journal of physiology and pharmacology. 99(4) |
ISSN: | 1205-7541 |
Popis: | Erythropoietin (EPO) is a cytokine originally used for its effects on the hematopoietic system, and is widely prescribed around the world. In the present study, the effects of EPO administration on p-aminohippurate (PAH, a prototype organic anion) pharmacokinetics and on the renal expression of PAH transporters were evaluated. Male Wistar rats were treated with EPO or saline (control group). After 42 h, PAH was administered, and plasma samples were obtained at different time points to determine PAH levels. PAH levels in renal tissue and urine were also assessed. The renal expression of PAH transporters was evaluated by Western blotting. EPO-treated rats showed an increase in PAH systemic clearance, in its elimination rate constant, and in urinary PAH levels, while PAH in renal tissue was decreased. Moreover, EPO administration increased the expression of the transporters of the organic anions evaluated. The EPO-induced increase in PAH clearance is accounted for by the increase in its renal secretion mediated by the organic anion transporters. The goal of this study is to add important information to the wide knowledge gap that exists regarding drug–drug interactions. Owing to the global use of EPO, these results are useful in terms of translation into clinical practice. |
Databáze: | OpenAIRE |
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