Kidneys plasma clearance

Plasma clearance is defined as the volume of plasma from which a substance is completely cleared by the kidneys per unit time (ml/min). Calculation of the plasma clearance of certain substances can be used to determine ... 

In order to use the plasma clearance of a substance to determine the effective rate of plasma flow (ERPF) through the kidneys, the following criteria regarding the substance must be met ... 

A substance that fulfills these criteria is para-aminohippuric acid (PAH). All of the PAH not filtered at the glomerulus is secreted by the proximal tubule. The net effect is that all of the plasma flowing through the nephrons is completely cleared of PAH. It is important to note that about 10 to 15% of the total renal plasma flow supplies regions of the kidneys that are not involved with filtration or secretion. Consequently, this plasma cannot be cleared of PAH. Therefore, the plasma clearance of PAH provides a measurement of the effective renal plasma flow, that is, the volume of plasma that actually flows through the nephrons. The ERPF is normally about 625 ml/ min. (This value is based on a renal blood flow of about 1.1 1/min and a hematocrit of about 42.)... 

The initial t for MeHg in plasma is brief (15 min.) while the second half-time is quite long (1.2 days) relative to all other pollutants in this report. The V is greater than that of body water and this is consistent with localization in RBC s, muscle and kidney. The clearance is one-half that of PAH. If other forms of Pt are as difficult to model pharmacokinetically and have the same implications as the results of this model, these heavy metal compounds might be troublesome. The slow removal of cis-Pt from the plasma (3-phase) has been noted previously in dogs and rats (22) it is 17.5 days in the shark. 

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... 

Excretion - Ertapenem is eliminated primarily by the kidneys. The mean plasma half-life in healthy young adults is approximately 4 hours, and the plasma clearance is approximately 1.8 L/hour. 

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. 

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. 

As expected, renal dysfunction is associated with an increase in volume of distribution, a decrease in plasma clearance (1.6 versus 2.4 ml/kg/minute), and an increase in half-hfe (263 versus 137 minutes) compared with patients with normal renal function (14). In the latter study there was no statistically significant prolongation of the mean duration of action of pipecuronium, but there was a much greater variation in those with renal insufficiency, with 25% recovery times (after 0.07 mg/kg) of 30-267 minutes (controls 55-198 minutes). These patients were also undergoing renal transplantation and most of the replacement kidneys would be expected to have some function and some glomerular excretion of pipecuronium. Prolongation of pipecuronium blockade should be expected in patients with renal insufficiency. 

Rifampicin enhances the catabolism of many glucocorticoids. For example, it increases the plasma clearance of prednisolone by 45 % and may reduce the amount of drug available to the tissues by as much as 66% (SEDA-8,288). Glucocorticoid therapy for concomitant diseases should therefore be adjusted in the light of plasma concentrations and clinical effects during rifampicin treatment (SEDA-10,272). For example, rejection of a kidney transplant occurred after 7 weeks of rifampicin therapy (109). 

Nicotine has low plasma protein binding (<5%) and a large volume of distribution (2-3 L/kg). It is eliminated mainly by hepatic metabolism, although some metabolism occurs in the lungs and kidneys. The main metabolites are cotinine (15% of the dose) and trans-3-hy-droxycotinine (45% of the dose). Only 10% of the absorbed dose is excreted unchanged in urine. In healthy adult smokers, nicotine has an apparent elimination half-life of 1-2 h and the average plasma clearance is 1.2 h (93). 

TABLE 16.2 Plasma Clearance of Merepenem in Isolated Perfused Rat Liver, Kidneys, Gut. and Lung... 

With the metabolism of merepenem as an example, perfused organ studies in the rat identihed the kidney as the major organ of metabolism (Table 16.2). Subsequently, it was established that fresh rat kidney slices and homogenates could be used in vitro. Cross-species studies showed that the rate of metabolism in rat kidney preparations was three- to fourfold higher than in human kidney (Table 16.3). These data predicted that the plasma clearance... 

Chronic renal disease may also affect metabolism, not necessarily because of impaired metabolism in the kidney, but because of an indirect effect of renal failure on liver metabolism. For example, in animals with renal failure it was observed that there was a decrease in hepatic cytochromes P-450 content, and consequently zoxazolamine paralysis time and ketamine narcosis time were prolonged. Cardiac failure may also affect metabolism by altering hepatic blood flow. However even after heart attack without hypotension or cardiac failure, metabolism may be affected. For example, the plasma clearance of lidocaine is reduced in this situation. Other diseases such as those which affect hormone levels hyper- or hypo-thyroidism, lack of or excess growth hormone, and diabetes can alter the metabolism of foreign compounds. 

After intravenous injection, the Tc(III)-DMSA complex is taken up in the renal parenchyma (24% at 1 h), showing high cortical affinity (Lin et al. 1974). Uptake is related to renal cortical perfusion the plasma clearance half-time in patients with normal kidney function is 56 min (Enlander et al. 1974). 

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). 

When Tc-EC was compared with Tc-MAG3, it showed a higher plasma clearance and considerably lower activity in the liver there was no significant activity in bowel and gallbladder even in patients with impaired kidney function (Verbruggen et al. 1992). 

With the notable exceptions of fosinopril and spirapril (which display balanced elimination by the liver and kidneys), ACE inhibitors are cleared predominantly by the kidneys. Therefore, impaired renal function significantly diminishes the plasma clearance of most ACE inhibitors, and dosages of these drugs should be reduced in patients with renal impairment. Elevated plasma renin activity (PRA) renders patients hyperresponsive to ACE inhibitor-induced hypotension, and initial dosages of all ACE inhibitors should be reduced in patients with high plasma levels of renin (e.g., patients with heart failure, and salt-depleted patients). 

Absorption of topiramate is rapid and unaffected by food intake, with peak plasma concentrations being achieved approximately 2 hours after administration of a 400 mg dose. Metabolism of topiramate is not extensive and its oral plasma clearance is slow, with approximately 70% of an administered dose being eliminated unchanged by the kidneys. When used as monotherapy, topiramate has a... 

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