Hypothetical framework for enhanced renal tubular secretion of drugs in cystic fibrosis
| Autor: | D. Blowey, C. Woodland, Gideon Koren, Shinya Ito, M. Spino |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
medicine.medical_specialty
Ion Transport Cystic Fibrosis biology Chemistry Reabsorption Cystic Fibrosis Transmembrane Conductance Regulator Lumen (anatomy) General Medicine medicine.disease Models Biological Cystic fibrosis Cystic fibrosis transmembrane conductance regulator Excretion Kidney Tubules Endocrinology Chlorides Internal medicine medicine Chloride channel biology.protein Humans Pharmacokinetics Secretion Homeostasis |
| Zdroj: | Medical Hypotheses. 51:489-491 |
| ISSN: | 0306-9877 |
| DOI: | 10.1016/s0306-9877(98)90070-6 |
| Popis: | Several clinical studies demonstrate reduced serum concentrations of renally excreted drugs in patients with cystic fibrosis (CF). To explain this phenomenon, we propose a model supporting increased proximal tubular secretion of certain drugs in individuals with CF. We hypothesize that the chloride channel located on the apical surface of renal proximal tubular cells and controlled by the cystic fibrosis transmembrane conductance regulator (CFTR) operates suboptimally in CF patients, and that the abnormal CFTR decreases Cl − reabsorption, resulting in an increased concentration of CI − in the tubular lumen. We postulate that, in an effort to maintain homeostasis, luminal CI − moves intracellularly in exchange for organic anions. The result of stimulating this anion exchanger is an increased rate of organic anion secretion by the renal tubule. Hence, due to enhanced tubular secretion, individuals with CF demonstrate increased tubular clearance of organic anion drugs, resulting in lower steady state serum concentrations. |
| Databáze: | OpenAIRE |
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