Glomerular filtration, drug excretion

The kidneys are located on the posterior part of the abdomen on either side of the spine, below the diaphragm, and behind the liver and stomach. They are bean-shaped and weigh approximately 150 grams (0.33 lb) each. The primary function of the kidneys is excretion. They work to excrete waste products through a series of steps involving glomerular filtration, secretion, and reabsorption. The kidneys also have several endocrine (e.g., production of erythropoietin and renin) and metabolic (e.g., vitamin D activation and drug metabolism) functions. 

The renal excretion of drugs depends on glomerular filtration, tubular secretion, and tubular absorption. A twofold increase in glomerular filtration occurs in the first 14 days of life [36], The glomerular filtration rate continues to increase rapidly in the neonatal period and reaches a rate of about 86 mL/min per 1.73 m2 by 3 months of age. Children 3-13 years of age have an average clearance of 134 mL/min per 1.73 m2 [37]. Tubular secretion approaches adult values between 2 and 6 months [11], There is more variability observed in maturation of tubular reabsorption capacity. This is likely linked to fluctuations in urinary pH in the neonatal period [38],... 

Renal elimination is primarily by glomerular filtration. Parent drug and metabolites are excreted primarily by the kidney however, urinary excretion... 

It does not inhibit cytochrome P450. Gatifloxacin is excreted as unchanged drug primarily by the kidney. Gatifloxacin undergoes glomerular filtration and tubular secretion. 

Excretion is by glomerular filtration, largely as unchanged drug thus, high urine levels are attained. Aminoglycosides are removed by hemodialysis (4 to 6 hours removes approximately 50%) and peritoneal dialysis (range, removal of 23% in 8 hours to only 4% in 22 hours). 

Renal elimination of foreign compounds may change dramatically with increasing age by factors such as reduced renal blood flow, reduced glomerular filtration rate, reduced tubular secretory activity, and a reduction in the number of functional nephrons. It has been estimated that in humans, beginning at age 20 years, renal function declines by about 10% for each decade of life. This decline in renal excretion is particularly important for drugs such as penicillin and digoxin, which are eliminated primarily by the kidney. 

Metabolites of the cholinesterase inhibitors and in some instances significant amounts of the parent compound are eliminated in the urine. Renal excretion is very important in the clearance of agents such as neostigmine, pyridostigmine, and edrophonium. This is demonstrated by a twofold to threefold increase in elimination half-lives for these drugs in anephric patients. Renal elimination is largely the result of glomerular filtration but probably also involves, at least in the case of quaternary amines, secretion via the renal cationic transport system. 

Nitrofurantoin is administered orally and is rapidly and almost completely absorbed from the small intestine only low levels of activity are achieved in serum because the drug is rapidly metabolized. Relatively high protein binding (about 70%) also affects serum levels, reducing potential for systemic toxicity and alteration of intestinal flora. Relative tissue penetration is much lower than other antimicrobials for UTIs, and therefore, nitrofurantoin is not indicated in the therapy of infections such as pyelonephritis and renal cortical or perinephric abscesses. Nitrofurantoin is rapidly excreted by glomerular filtration and tubular secretion to yield effective urinary levels. In moderate to severe renal dysfunction, toxic blood levels may occur while urinary levels may be inadequate. The drug is inactivated in the liver. 

Chloramphenicol is inactivated in the liver by glu-curonosyltransferase and is rapidly excreted (80-90% of dose) in the urine. About 5 to 10% of the administered drug is excreted unchanged. Renal elimination is by tubular secretion and glomerular filtration. Other degradation pathways are known to exist and may account for some of the toxicity seen in neonates and children. 

The polymyxins are slowly excreted by glomerular filtration the slow elimination rate is due to binding in tissues. Elimination is decreased in patients with renal disease, and drug accumulation can lead to toxicity. Sodium coUstimethate, the parenteral preparation, binds less to tissue and is excreted faster than the free base. 

Pyrazinamide is well absorbed from the GI tract and is widely distributed throughout the body. It penetrates tissues, macrophages, and tuberculous cavities and has excellent activity on the intracellular organisms its plasma half-life is 9 to 10 hours in patients with normal renal function. The drug and its metabolites are excreted primarily by renal glomerular filtration. 

Cidofovir has extremely low oral bioavailability and so must be administered intravenously. Although the plasma elimination half-life averages 2.6 hours, the diphosphate form of the drug is retained within host cells and has an intracellular half life of 17 to 65 hours. A phosphocholine metabolite has a half-life of approximately 87 hours and may serve as an intracellular reservoir of the drug. Cidofovir is not significantly metabolized and is excreted unchanged by the kidney. Glomerular filtration and probenecid-sensitive tubular secretion are responsible for cidofovir elimination. 

Methotrexate is well absorbed orally and at usual dosages is 50% bound to plasma proteins. The plasma decay that follows an intravenous injection is triphasic, with a distribution phase, an initial elimination phase, and a prolonged elimination phase. The last phase is thought to reflect slow release of methotrexate from tissues. The major routes of drug excretion are glomerular filtration andl active renal tubular secretion. 

Most of the drug is excreted unchanged by the kidney by tubular secretion and glomerular filtration.9-Carboxymethoxymethylguanine is the only significant metabolite of acyclovir recovered from the urine. 

After oral administration, it is rapidly absorbed and is distributed in various body tissues including CSF. It is excreted largely unchanged in urine by glomerular filtration. It is used for treatment of multidrug resistant tuberculosis with other primary drugs. It is also used in acute urinary tract infections caused by susceptible microorganisms. 

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 may contribute 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 is excreted in feces. Doxycycline and tigecycline, in contrast to other tetracyclines, are eliminated by nonrenal mechanisms, do not accumulate significantly and require no dosage adjustment in renal failure. 

Drugs of the neomycin group are poorly absorbed from the gastrointestinal tract. After oral administration, the intestinal flora is suppressed or modified, and the drug is excreted in the feces. Excretion of any absorbed drug is mainly through glomerular filtration into the urine. 

A portion of absorbed drug is acetylated or glucuronidated in the liver. Sulfonamides and inactive metabolites are then excreted into the urine, mainly by glomerular filtration. In significant renal failure, the dosage of sulfonamide must be reduced. 

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