Clearance renal

FIGURE 2.8 Determination of relative clearance of dextran as a function of solute size. Please note that Stokes radius (left curve) will yield too low a value for the renal clearance barrier. [Reproduced from Hagel et al. (1993), with permission.]... 

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). 

Total drug clearance is the sum of nonrenal clearance and renal clearance (Clren). According to the MDRD-2 formula, the estimated GFR (eGFR) is a function of serum creatinine (SCr in mg/dl) and age (Age in years). It has the unit ml/min per 1.73 mA2. 

The renal clearance can be under estimated in the case of renal drug metabolism. The total drug clearance depends on bioavailability. Therefore, the most reliable estimate for the fraction eliminated by the renal route (fren) is given by the normal clearance (Clnorm) and drug clearance in case of acute and/ or chronic renal failure (Clfail), or from half-lives (Tl/2norm) and (Tl/2fail). 

To combat this syndrome the physician may prescribe IV sodium chloride and a potent diuretic, such as furosemide. When used together these two drugs markedly increase calcium renal clearance and reduce hypercalcemia... 

The rate of urine amylase excretion is a sensitive reflection of the amylase released into the blood. The urine amylase remains abnormal 1-2 weeks after the serum returns to normal because the renal clearance of amylase rises 3-fold in acute pancreatitis and takes 1-2 weeks to return to normal. In pancreatitis, a number of investigators have reported a higher percentage of urinary amylase elevations, as contrasted with serum amylase elevations, particularly when the urinary amylase output over an interval is measured. Random urine collections for one, two and 24 hours are 792-4264 (2926 1074 S.D.) units per 24 hours. However, the wide range of normals make interpretation of results difficult. Of 107 patients with elevated serum or urine amylases, 16 were found to have a normal pancreas at operation (78). 

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. 

Warshaw and Fuller (80) studied the specificty of increased renal clearance of amylase in acute pancreatitis. They established 3.1% 1.1 S.D. for the Cam/Ccr ratio in normal persons. In patients with acute pancreatitis this ratio rises regularly and significantly to 9.8 3.5 S.D. They suggested that renal... 

Despite their potential health-promoting effects as dietary antioxidants, the fate of betalains in humans has been poorly studied. Betalain bioavailability was first demonstrated in humans by the appearance of betacyanins in urines after ingestion of beetroot extract" and red beet juice," indicating that these compounds are indeed absorbed. Although intact betacyanins (betanin and isobetaiun) appeared rapidly in human urine with a maximum excretion rate observed within 2.5 to 8 hr," betacy-anin recoveries in human urine were usually low (< 1% of the dose) over 24 hr postdose, suggesting that either the bioavailabifity of betacyaiuns from red beetroot is low or that renal clearance is a minor excretion route for these compounds. 

The area under the PCP concentration-time curve (AUC) from the time of antibody administration to the last measured concentration (Cn) was determined by the trapezoidal rule. The remaining area from Cn to time infinity was calculated by dividing Cn by the terminal elimination rate constant. By using dose, AUC, and the terminal elimination rate constant, we were able to calculate the terminal elimination half-life, systemic clearance, and the volume of distribution. Renal clearance was determined from the total amount of PCP appearing in the urine, divided by AUC. Unbound clearances were calculated based on unbound concentrations of PCP. The control values are from studies performed in our laboratory on dogs administered similar radioactive doses (i.e., 2.4 to 6.5 pg of PCP) (Woodworth et al., in press). Only one of the dogs (dog C) was used in both studies. 

When we calculated systemic and renal clearance based on the area under the unbound PCP concentration-time curve, we found essentially no change in these parameters compared to the control studies without antibody (Woodworth et al., in press) (figure 6). 

CF patients have larger volumes of distribution of many antibiotics due to an increased ratio of lean body mass to total body mass and lower fat stores. CF patients also have an enhanced total body clearance, although the exact mechanism has not been determined. Increased renal clearance, increased glomerular filtration rate, decreased protein binding, increased tubular secretion, decreased tubular reabsorption, extrarenal elimination, and increased metabolism have all been proposed as possible reasons for the increased clearance. 

Topotecan inhibits topoisomerase I to cause single-strand breaks in DNA. The pharmacokinetics of topotecan can be described by a two-compartment model, with a terminal half-life of 80 to 180 minutes, with renal clearance accounting for approximately 70% of the clearance.19 Topotecan has shown clinical activity in the treatment of ovarian and lung cancer, myelodysplastic syndromes, and acute myelogenous leukemia. The intravenous infusion may be daily for 5 days or once weekly. Side effects include myelosuppression, mucositis, and diarrhea. 

Bleomycin Antitumor antibiotic Renal clearance Pulmonary fibrosis... 

Example. In the example plotted in Fig. 6, the amount of drug excreted over the 0- to 0.5-hour interval was 37.5 mg. If the plasma concentration at 0.25 hour (the middle of the interval) was lOpg/mL, what was the renal clearance rate From Eq. (18),... 

Araki S, Aono H, Yokoyama K, et al. 1986. Filterable plasma concentration, glomerular fdtration, tubular reabsorption and renal clearance of heavy metals and organic substances in metal workers. Arch Environ Health 41 216-221. 

Intravenous administration 24 h Nontoxic Renal clearance No accumulation in liver and lungs [120]... 

Intravenous administration 30 min Non toxic Agglomeration-dependent renal clearance [122]... 

Intravenous administration 7 d Nontoxic Renal clearance No active secretion [124]... 

Below 0 Intestinal and CNS permeability problems. Susceptible to renal clearance. If MW < 300, may be absorbed by the slower paracellular route. 

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