Drug elimination glomerular filtration

Hepatic clearance is termed restrictive in this case, since it is limited by protein binding. This situation is analogous to the elimination of drugs by glomerular filtration. Drugs that are restrictively eliminated have extraction ratios < 0.3. 

Elimination. Glomerular filtration, tubular secretion and reabsorption are low in the neonate (even lower in preterm babies) only reaching adult values in relation to body surface area at 2-5 months. Therefore drugs that are eliminated by the kidney (e.g. aminoglycosides, penicillins, diuretics) must be given in reduced dose after about 6 months. 

Other organs have the abihty to eliminate drugs or metabolites from the body. The kidney can excrete drugs by glomerular filtration or by such active processes as proximal mbular secretion. Drugs also can be eliminated via bile produced by the liver or air expired by the lungs. 

The glomerular filtration rate (GFR) in normal males is estimated to be 125mL/min, and the results of the example calculation suggest that the drug is cleared by GFR. If the RCR had been less than 125 mL/min, tubular reabsorption of the drug would have been suspected. If it had been greater than 125 mL/min, tubular secretion would have been involved in the drug elimination. 

After either oral or intravenous administration of ondansetron to laboratory animals the elimination of the drug is rapid. The short elimination half-lives t ji Table 7.7) reflect the high plasma clearance (CLp) in these species. Renal clearance (CLr) is below glomerular filtration rate, indicating that the major component of systemic clearance is metabolism. Ondansetron is rapidly absorbed after oral administration, peak concentrations in plasma being achieved within 40 min of dosing. However, the oral bioavailability is low. The similarity between concentrations of total drug-related material in plasma after oral and intravenous doses indicates that the low... 

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

Entecavir is predominantly eliminated by the kidney with urinary recovery of unchanged drug at steady state ranging from 62% to 73% of the administered dose. Entecavir undergoes both glomerular filtration and net tubular secretion. 

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. 

When probenecid (ColBENEMID) is given in sufficient amounts, it will block the active reabsorption of uric acid in the proximal tubules following its glomerular filtration, thereby increasing the amount of urate eliminated. In contrast, low dosages of probenecid appear to compete preferentially with plasma uric acid for the proximal tubule anionic transport system and thereby block its access to this active secretory system. The uricosuric action of probenecid, however, is accounted for by the drug s ability to inhibit the active reabsorption of filtered urate. 

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. 

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. 

Amantadine is rapidly and completely absorbed from the gastrointestinal tract, and peak blood levels are achieved in 2 to 5 hours. The serum half-life of amantadine averages 17 hours in young adults and 29 hours in the elderly. Most of the drug (90%) is eliminated unchanged by glomerular filtration and tubular secretion. 

Orally administered oseltamivir phosphate is rapidly absorbed and converted by hepatic esterases to oseltamivir carboxylate. Approximately 80% of an oral dose reaches the systemic circulation as oseltamivir carboxylate, with peak plasma concentrations achieved within 2.5 to 5 hours. The plasma elimination half-life of oseltamivir carboxylate is 7 to 9 hours. Elimination of the parent drug and its active metabolite occurs primarily by active tubular secretion and glomerular filtration. 

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. 

Elimination Reduced renal plasma flow Reduced glomerular filtration rate Decreased tubular secretion function Decreased renal elimination of drugs and metabolites marked interindividual variation... 

In congestive heart failure the drug elimination is retarded due to decreased perfusion and congestion of liver, also reduced glomerular filtration and increased tubular reabsorption. 

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