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PHARMACOKINETIC OF RENAL FAILURE THERAPY

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Abstract (2. Language): 
Renal failure (loss of kidney normal functionality) is characterized by the reduction in the excretory and regulatory functions of the kidney. It usually occurs at the terminal stages of the disease processes. The Kidney is the primary organ responsible for the excretion of drugs and their metabolites. Risk factors for the development of nephrotoxicity for selected high-risk therapies, e.g. aminoglycosides, NSAIDs, amphotericin B, antineoplastics, ACE inhibitors, angiotensin II receptor blockers. Beside these, drug administered along with certain known nephrotoxic compounds as well as administration of drugs in hepatic disorders may also progressively influence kidney functioning. Methods that have been used to evaluate kidney function in veterinary medicine include determination of serum creatinine and BUN concentrations. Impaired renal function alters pharmacokinetics of drugs, which are mainly eliminated via kidney. Changes arising from renal impairment are decrease in renal excretion, or possibly renal metabolism. Other changes include changes in absorption, hepatic metabolism, plasma protein binding and drug distribution. The pathophysiological mechanism responsible for alterations in drug disposition, especially metabolism and renal excretion is the accumulation of uraemic toxins that may modulate cytochrome P450 enzyme activity and decrease glomerular filtration as well as tubular secretion. Dosage regimen adjustment is mainly considered in renal diseases, when the drug is mainly (at least 70% of the dose) excreted by the kidney either unchanged or as an active metabolite or the therapeutic window of the drug or the metabolite is narrow.

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