Kidneys renal clearance

Galanthamine is metabolized in the liver small amounts of the active metabolites epigalan-thamine and galanthaminone can be measured in the plasma. These metabolites are 130-fold less potent than galanthamine. Negligible quantities of these two metabolites can also be detected in urine. Galanthamine is cleared from the body by excretion in the kidneys renal clearance has been estimated at 0.084 1/kg/h. 

From either a Cp or In Cp versus time plot, one feature is immediately clear the drug concentration drops over time. This process is called elimination and is determined by clearance (CL). Clearance is the process of removal of drug from the bloodstream. As was discussed in Chapter 3, clearance occurs primarily either through filtration of a drug by the kidneys (renal clearance, CLR) or metabolism of a drug in the liver by the action of enzymes (hepatic clearance, CLH). Other clearance processes are possible, but CLR and CLh normally comprise the large majority of total clearance (CLy or simply CL) (Equation 7.6). 

CSF if the meninges are inflamed. Penicillins are organic acids and their rapid clearance from plasma is due to secretion into renal tubular fluid by the anion transport mechanism in the kidney. Renal clearance therefore greatly exceeds the glomerular filtration rate (127 ml/min). The excretion of penicillin can be usefully delayed by concurrently giving probenecid which competes successfully for the transport mechanism. Dosage of penicillins may should be reduced for patients with severely impaired renal function. 

After intravenous injection, Tc-DTPA penetrates capillary walls to enter the extra-vascular space within 4 min (McAfee et al. 1979). Because of its hydrophilicity and negative charge, Tc-DTPA is excluded from cells and is confined to the extracellular space. Tc-DTPA is removed from the circulation exclusively by the kidneys renal clearance is unaffected by urine flow and by the administration of probenecid (Klopper et al. 1972). However, only the filtered fraction (20%) of the total renal plasma flow is excreted by glomerular filtration (Barbour et al. 1976). 

Dynamic renography allows estimation of three parameters of renal function blood flow to the kidney renal clearance (Prigent et al. 1999 Rutland 1985 PiEPSz et al. 1998), i.e., the extraction of a tracer from the blood, when estimation of relative clearance occurs as in differential renal function (DRF) and the drainage function or excretion from the kidney. 

The kidney function confers high impact on diug kinetics when a high fraction (fren) of the diug dose (D) is eliminated in urine (Aurine). The renal fraction (fren) can be underestimated when bioavailability (F) is neglected. The renal clearance, however, can be derived from the amount eliminated by the renal route (Aurine) independent from bioavailability (F). 

The study of the mechanism of urinary excretion of amylase and the amylase clearance has been the subject of many studies in recent years. Levitt et. al (79) studied the renal clearance of amylase in renal insufficiency, acute pancreatitis and macro-amylasemia. In acute pancreatitis, the kidney cleared amylase at a markedly increased rate. The ratio of the amylase clearance rate to the creatinine clearance rate (Cgm/Ccr) averaged 3 times normal early in the course of acute pancreatitis, and this elevation could persist after the serum amylase returned to normal. Comparison of an lase clearance to creatinine clearance was to minimize irrelevant changes due to variation in renal function. The increased clearance of amylase makes the urinary amylase a more sensitive indicator of pancreatitis. 

Clearance is defined as the fraction of the volume of distribution Vp that is cleared of the drug per unit of time. In the case of elimination from the kidneys, the clearance provides a measure for the effectiveness of renal elimination with respect to the dmg under study. 

Although determination of creatinine clearance rate is a standard clinical procedure, it is difficult to carry out mainly because accurate collection of total urine output over a 24-hour period is required. It can never be certain that this requirement has been met. Since creatinine is produced continuously in muscle and is cleared by the kidney, renal failure is characterized by elevated serum creatinine levels. The degree of elevation is directly related to the degree of renal failure—if it is assumed that the production of creatinine in the muscle mass is constant and that renal function is stable. When these assumptions are valid, there is a direct relationship between serum creatinine level and kanamycin half-life, as shown in Fig. 9. The equation of the line in Fig. 9 is... 

The most common adverse effects involve the GI system (gastritis, bleeding, and perforation), kidneys (renal papillary necrosis, reduced creatinine clearance [CLcr]), cardiovascular system (sodium and fluid retention, increased blood pressure), and CNS (impaired cognitive function, headache, dizziness). 

No single toxin is responsible for all of the signs and symptoms of uremia observed in stage 4 or 5 CKD. Toxins accumulate as a result of increased secretion, decreased clearance secondary to reduced metabolism within the kidney, and/or decreased renal clearance of by-products of protein metabolism. 

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... 

Kidney failure not only decreases renal clearance of nicotine and cotinine, but also metabolic clearance of nicotine (Molander et al. 2000). Metabolic clearance of nicotine is reduced by 50% in subjects with severe renal impairment compared to healthy subjects. It is speculated that accumulation of uremic toxins may inhibit CYP2A6 activity or downregulate CYP2A6 expression in liver. Hepatic metabolism of several drugs is reduced in kidney failure, mainly via downregulation of CYP enzymes and/or inhibition of transporters (Nolin et al. 2003). 

In vitro stndies have shown that there are distinct transport systems for both baso-lateral and apical uptake of nicotine (Takami et al. 1998). Nicotine has been shown to be actively transported by kidney cells, most likely by the organic ion transporter OCT2 (Zevin et al. 1998 Urakami et al. 1998). Cimetidine decreases renal clearance of nicotine by 47% in nonsmoking volunteers (Bendayan et al. 1990). This is consistent with the inhibition of basolateral uptake by cimetidine detected in vitro. Mecamylamine reduces renal clearance of nicotine in smokers dosed with intra-venons nicotine when urine is alkalinized, but not when nrine is acidified (Zevin et al. 2000). 

As mentioned previously, renal failure markedly reduces total renal clearance, as well as metabolic clearance of nicotine and cotinine (Molander et al. 2000). Reduction of renal clearance is correlated with the severity of kidney failure renal clearance is reduced by half in mild renal failure, and by 94% in severe renal impairment. Markedly elevated levels of serum nicotine have been detected in smoking patients with end-stage renal disease undergoing hemodialysis (Perry et al. 1984). This is explained not only by reduced renal clearance, but also by lower metabolic... 

The organs of extraction are generally the liver (hepatic clearance - metabolism and biliary excretion CIh) and the kidney (renal excretion, CIr) and the values can be summed together to give an overall value for systemic clearance (Cls) ... 

A typical clearance profile and curve-fitting of these bioconjugates in a rat with normal renal function is shown in Fig. 16. The time constant is the relevant quantifiable measure for how fast the agent clears from the vascular system. Figs. 17 and 18 compare the plasma clearance profile of different fluorescein conjugates in normal and ligated rat kidneys. The clearance profile followed the... 

Renal function impairment Because these agents are excreted primarily via the kidneys, decreased clearance may occur reduced dosage may be necessary. P.806... 

However, in patients with renal failure there is a strange and currently unexplained observation in relation to non-renal clearance. If this is measured for some compounds it also is found to be depressed even though it is the kidney that is diseased and not the liver The picture becomes a little clearer if the same non-renal (presumed hepatic) clearance is measured again in patients after renal dialysis when the hepatic clearance has been found to have risen to control values. Recent animal experiments have demonstrated that the circulating inhibitor of hepatic cytochrome P450 may be parathyroid hormone. Parathyroidectomy of rats with chronic renal failure prevented the reduction in liver cytochrome activity (see Michaud et al., 2006). 

Procainamide is eliminated by hepatic metabolism to NAPA and by renal elimination. Its half-life is only 3-4 hours, which necessitates frequent dosing or use of a slow-release formulation (the usual practice). NAPA is eliminated by the kidneys. Thus, procainamide dosage must be reduced in patients with renal failure. The reduced volume of distribution and renal clearance associated with heart failure also require reduction in dosage. The half-life of NAPA is considerably longer than that of procainamide, and it therefore accumulates more slowly. Thus, it is important to measure plasma levels of both procainamide and NAPA, especially in patients with circulatory or renal impairment. 

Digoxin is not extensively metabolized in humans almost two thirds is excreted unchanged by the kidneys. Its renal clearance is proportional to creatinine clearance and the half-life is 36-40 hours in patients with normal renal function. Equations and nomograms are available for adjusting digoxin dosage in patients with renal impairment. 

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