Drug elimination renal excretion

Excretion of drugs or chemicals from the body can occur through biliary, intestinal, puhnonary, or renal routes. Although each of these represents a possible mechanism of drug elimination, renal excretion is a major pathway for the ehmination of most water-soluble drugs or metabohtes and is important m TDM. Alterations in renal function may have a profound effect on the clearance and apparent half-life of the parent compound or its active metabolite(s) decreased renal function causes elevated serum drug concentrations and increases the pharmacological response. 

Fluoxetine is rapidly and completely absorbed orally, reaching a peak in 6-8 h. Food does not affect absorption. Fluoxetine is N-demethylated in the liver to an active metabolite, norfluoxetine, and many other minor inactive metabolites. Both fluoxetine and norfluoxetine are then conjugated prior to excretion. Protein binding is 94%. The volume of distribution is estimated to be 11-88.41 kg Approximately 2.5% of the drug is renally excreted unchanged and 10% as the norfluoxetine metabolite. A total of 65% of radiolabeled fluoxetine is recovered in the urine after 35 days and 15% is recovered in the feces. The elimination half-life of fluoxetine is 48-72 h, averaging almost 70 h. The half-life of norfluoxetine is 7-9 days. The elimination half-lives for both are prolonged in patients with hepatic disease. 

Elimination J. Renal blood flow i GFR i ARTS J. No. functioning nephrons T ty2 renally excreted drugs... 

It is eliminated primarily by renal excretion as unchanged drug dosage adjustment is required in patients with renal dysfunction. 

Peak plasma levels are reached about 1.5 h after oral ingestion, the maximum concentrations being in the order of 2 - 3 ng equivalents/ml (parent drug + metabolites) for an oral 1 mg dose. The elimination from the plasma is biphasic and proceeds with mean half-lives of 6 h (a-phase) and 50 h ((3-phase). Similar elimination half-lives are obtained from the urinary excretion. The cumulative renal excretion is practically the same after oral and intravenous administration and amounts to 6 - 7 % of the radioactivity dosed. The main portion of the dose, either oral or intravenous, is eliminated by the biliary route into the faeces. The kinetics of bromocriptine has been demonstrated to be linear in the oral dose range from 2.5 to 7.5 mg. 

The elimination half life of a drug will thus increase if the volume of distribution is increased as for lipophilic drugs in the elderly or if the clearance is affected, the latter mainly hepatic metabolism or renal excretion. 

Clearance refers to the elimination of drug from the body. It is defined as the volume of blood which is completely cleared of drug per unit time. The drug can be eliminated via excretion through kidneys, and/or metabolism in liver, or through other routes such as saliva, milk, sweat, etc. The clearance associated with the kidney is called the renal clearance (C1r), and the clearance associated with other routes including metabolism is known as non-renal... 

Biotransformation involves the chemical alteration of a molecule to alter its effects. This often terminates the pharmacological effects of a drug, but active metabolites are produced in some cases. Biotransformation also changes the ease with which a drug is eliminated. This involves conversion of the drug to a more hydrophilic metabolite that enhances renal excretion. Although this process pertains to most drugs, it probably... 

Excretion - Miglitol is eliminated by renal excretion as unchanged drug. Following a 25 mg dose, more than 95% of the dose is recovered in the urine within 24 hours. The elimination half-life from plasma is approximately 2 hours. 

The main route of elimination is via hepatic excretion into bile some enterohepatic recirculation may occur. The drug has a very low plasma clearance with negligible renal excretion. Neither amiodarone nor its metabolite is dialyzable. 

Pharmacokinetics Gabapentin bioavailability is not dose-proportional. It circulates largely unbound (less than 3%) to plasma protein and is eliminated from the systemic circulation by renal excretion as unchanged drug it is not appreciably metabolized. 

Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug, with a mean elimination half-life of 6.3 hours in subjects with normal renal function. Mean renal clearance was estimated to be 67 to 80.9 mL/min in young healthy subjects. Because pregabalin is not bound to plasma proteins, this clearance rate indicates that renal tubular reabsorption is involved. Pregabalin elimination is nearly proportional to Ccr. 

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. 

Carboplatin (Paraplatin) is an analogue of cisplatin. Its plasma half-life is 3 to 5 hours, and it has no significant protein binding. Renal excretion is the major route of drug elimination. 

Elimination of clonidine is 65% by renal excretion and 35% by liver metabolism, while guanfacine and its metabolites are excreted primarily in the urine, with approximately 50% as unchanged drug. These differences in elimination may account for differences in the pharmacodynamic properties of the two drugs. The behavioral effects of clonidine last only 3 to 6... 

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