Renal insufficiency drug excretion

Oral bisphosphonates are poorly absorbed (less than 5%). Taking them in the presence of food or calcium supplementation further reduces absorption. After absorption, bisphosphonate uptake to the primary site of action is rapid and sustained. Once attached to bone tissue, bisphosphonates are released very slowly. These drugs are not metabolized and are excreted renally. They are not recommended for use in patients with renal insufficiency. 

The sterile peritoneal dialysis solutions are infused continuously into the abdominal cavity, bathing the peritoneum, and are then continuously withdrawn. The purpose of peritoneal dialysis is to remove toxic substances from the body or to aid and accelerate the excretion function normal to the kidneys. The process is employed to counteract some forms of drug or chemical toxicity as well as to treat acute renal insufficiency. Peritoneal dialysis solutions contain glucose and have an ionic content similar to normal extracellular fluid. Toxins and metabolites diffuse into the circulating dialysis... 

Although the pharmacokinetics of rifaximin in patients with renal insufficiency has not been specifically studied, its very low renal excretion makes any dose adjustment unnecessary. The same holds true for patients with hepatic insufficiency. In fact, the mean peak drug plasma concentrations (i.e. 13.5 ng/ml) detected in subjects with hepatic encephalopathy patients given rifaximin 800 mg 3 times daily for 7 days [34, 108] were not dissimilar to those found in healthy subjects [102] and patients with IBD [98], Indeed, in all the trials performed in this condition the drug has been well tolerated [33, 77],... 

Oral colchicine causes dose-dependent GI adverse effects (nausea, vomiting, and diarrhea) in 50% to 80% of patients before relief of the attack. Non-GI adverse effects include neutropenia and axonal neuromyopathy, which may be worsened in patients taking other myopathic drugs (e.g., statins) or in those with renal insufficiency. Colchicine should not be used concurrently with macrolide antibiotics (especially clarithromycin) because reduced biliary excretion may lead to increased plasma colchicine levels and agranulocytosis. 

Impaired liver function, either due to primary disease or secondary to cardiac failure, may cause drug accumulation (Tl). Renal insufficiency may have two effects changes in the binding properties of plasma protein secondary to uremia can occur (R6, SI 6), or the drug and its metabolites may accumulate owing to impaired urinary excretion. 

Excretion - Unchanged drug is excreted (approximately 50%) in the urine, 8% to 15% as metabolites and 20% to 22% unchanged in the feces. Marked accumulation may occur with renal insufficiency. Ethambutol is not significantly removed by hemodialysis. 

While essentially all ACE inhibitors have a similar mechanism of action and therefore exhibit similar efficacy in the treatment of hypertension and congestive heart failure, these drugs differ slightly in their pharmacokinetic profiles. Enalapril, lisinopril, and quinapril are excreted primarily by the kidney, with minimal liver metabolism, while the other prodrug compounds are metabolized by the liver and renally excreted. Thus, in patients with renal insufficiency, the half-life of renally excreted ACE inhibitors is prolonged. In addition, patients with impaired liver func-... 

Heparin s action is terminated by uptake and metabolism by the reticuloendothelial system and liver and by renal excretion of the unchanged drug and its de-polymerized and desulfated metabolite. The relative proportion of administered drug that is excreted as unchanged heparin increases as the dose increases. Renal insufficiency reduces the rate of heparin clearance from the blood. 

The carbonic anhydrase inhibitors are well absorbed after oral administration. An increase in urine pH from the HC03 diuresis is apparent within 30 minutes, is maximal at 2 hours, and persists for 12 hours after a single dose. Excretion of the drug is by secretion in the proximal tubule S2 segment. Therefore, dosing must be reduced in renal insufficiency. 

Most of the drug is inactivated either by conjugation with glucuronic acid (principally in the liver) or by reduction to inactive aryl amines. Active chloramphenicol (about 10% of the total dose administered) and its inactive degradation products (about 90% of the total) are eliminated in the urine. A small amount of active drug is excreted into bile and feces. The systemic dosage of chloramphenicol need not be altered in renal insufficiency, but it must be reduced markedly in hepatic failure. Newborns less than a week old and premature infants also clear chloramphenicol less well, and the dosage should be reduced to 25 mg/kg/d. 

Nitrofurantoin is well absorbed after ingestion. It is metabolized and excreted so rapidly that no systemic antibacterial action is achieved. The drug is excreted into the urine by both glomerular filtration and tubular secretion. With average daily doses, concentrations of 200 mcg/mL are reached in urine. In renal failure, urine levels are insufficient for antibacterial action, but high blood levels may cause toxicity. Nitrofurantoin is contraindicated in patients with significant renal insufficiency. 

The highly polar ionic character of EDTA limits its oral absorption. Moreover, oral administration may increase lead absorption from the gut. Consequently, EDTA should be administered by intravenous infusion. In patients with normal renal function, EDTA is rapidly excreted by glomerular filtration, with 50% of an injected dose appearing in the urine within 1 hour. EDTA mobilizes lead from soft tissues, causing a marked increase in urinary lead excretion and a corresponding decline in blood lead concentration. In patients with renal insufficiency, excretion of the drug—and its metal-mobilizing effects—may be delayed. 

Blood urate concentrations can be increased because of reduced excretion of uric acid in patients taking ethambutol (390). This is probably enhanced by combined treatment with isoniazid and pyridoxine. Special attention should be paid when tuberculostatic drug combinations include pyrazinamide. However, severe untoward clinical effects are rare, except in patients with gout or renal insufficiency (391,392). 

Metformin has a half-life of 1.5-3 hours, is not bound to plasma proteins, is not metabolized, and is excreted by the kidneys as the active compound. As a consequence of metformin s blockade of gluconeogenesis, the drug may impair the hepatic metabolism of lactic acid. In patients with renal insufficiency, biguanides accumulate and thereby increase the risk of lactic acidosis, which appears to be a dose-related complication. 

Vancomycin is poorly absorbed from the intestinal tract and is administered orally only for the treatment of antibiotic-associated enterocolitis caused by Clostridium difficile. Parenteral doses must be administered intravenously. A 1 hour intravenous infusion of 1 g produces blood levels of 15-30 jig/mL for 1-2 hours. The drug is widely distributed in the body. Cerebrospinal fluid levels 7-30% of simultaneous serum concentrations are achieved if there is meningeal inflammation. Ninety percent of the drug is excreted by glomerular filtration. In the presence of renal insufficiency, striking accumulation may occur (Table 43-2). In functionally anephric patients, the... 

Tetracyclines are excreted mainly in bile and urine. Concentrations in bile exceed those in serum tenfold. Some of the drug excreted in bile is reabsorbed from the intestine (enterohepatic circulation) and contributes to maintenance of serum levels. Ten to 50 percent of various tetracyclines is excreted into the urine, mainly by glomerular filtration. Ten to 40 percent of the drug in the body is excreted in feces. Doxycycline, in contrast to other tetracyclines, is eliminated by nonrenal mechanisms, does not accumulate significantly in renal failure, and requires no dosage adjustment, making it the tetracycline of choice for use in the setting of renal insufficiency. 

Three agents are available ondansetron, granisetron, and dolasetron. The drugs have a long serum half-life of 4-9 hours and may be administered once or twice daily by oral or intravenous routes. The drugs undergo extensive hepatic metabolism and are eliminated by renal and hepatic excretion. However, dose reduction is not required in geriatric patients or patients with renal insufficiency. For patients with hepatic insufficiency, dose reduction may be required with ondansetron. 

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