Renal filtration

PEG (20 kDa) [43]. This demonstrates the strong hydrodynamic properties of PEGylated molecules. The increase in hydrodynamic radius significantly decreases renal clearance. Although the threshold of the molecular weight cut-off of renal filtration of protein is about 65 kDa, the 30-kDa PEG demonstrates minimal renal permeability [44]. 

Altered renal filtration, secretion, and/or absorption can have dramatic effects on the pharmacokinetics of a drug. The impact depends on the fraction of drug normally eliminated unchanged by the kidney and on the degree of renal insufficiency. 

Subsequent to the ingestion of iodine in various forms, I is absorbed by the small intestine and enters the blood. Two competing pathways are involved in the clearance of I from the blood renal filtration into urine and thyroidal uptake. The renal clearance rate for I (30-50 mL/minute) varies only with the glomerular filtration rate. However, the thyroidal 1 clearance rate is autoregulated to maintain an absolute thyroidal I uptake rate of approximately 100 jig I each day. To accomphsh this, the thyroidal I clearance rate may vary (3 to 100 mL/minute) depending on the concentration of I in the blood. 

Small molecules are eliminated from the body largely by means of drug metabolism enzymes in the liver and other tissues and by urinary excretion. Large molecules are also eliminated by renal and hepatic mechanisms. Proteins that are less than 40 to 50 kDa are cleared by renal filtration with little or no tubular reabsorption. Larger proteins are less likely to be filtered but may be subject to phagocytosis in hepa-tocytes and Kupfer cells in the liver. Protein biotransformation—denaturation, proteolysis, and oxidative metabolism—is also important. 

Renal Filtration (MW < 40-50 kDa) (cleared without reabsorption) metabolism Filtration transport metabohsm tubular reabsorption... 

Deen,W.M., M.J. Lazzara, and B.D. Myers. 2001. Structural determinants of glomerular permeability. Am. J. Physiol. Renal Physiol. 281 F579—596. Maack,T., C. Park, and M. Camargo. 1985. Renal filtration, transport and metabolism of proteins. In D. Seldin, and G. Giebisch (Eds.), The Kidney. 

Acetaminophen and other xenobiotic substances are metabolized by the formation of water-soluble glucuronides that are subsequently removed by renal filtration. When given in combination with stable isotopes such as 2H and 13C, the glucuronides isolated from urine that were analyzed with 3 mm NMR probes provided a chemical biopsy and a convenient means for assessing intermediary liver metabolism. 

Maack T, Johnson V, Kau ST, Figueiredo J, Sigulem D. Renal filtration, transport, and metabolism of low-molecular-weight proteins A review. Kidney Int 1979 16 251-70. 

Mannitol Stimulation of osmotic diuresis is possible using mannitol (10-20% solution). (128) Mannitol is neither metabolized in the body nor reabsorbed by the tubules and is excreted almost totally through the kidney. Renal circulation and renal filtration are raised, and by reducing tubular absorption (= osmotic diuresis), water excretion is increased ( diuresis starter ). The saluretic effect is, however, relatively small. In the case of restricted renal function, application of mannitol is contraindicated. If necessary, the mannitol test (i.v. injection of 75 ml of a 20% solution) can be carried out beforehand. With enhanced diuresis of > 40 ml/hr, the kidneys still function adequately, so that it is possible to stimulate osmotic diuresis by means of a mannitol infusion. 

Although diastereoisomers, both quinine and quinidine, have similar physical properties (Fig. 18). In clinical studies, the renal clearance of quinidine was fourfold greater than that of quinine (57). No stereoselective differences in plasma protein binding were observed. The renal filtration and passive reabsorption of these two diastereoisomers should be similar since the compounds have similar octanol-water partition coefficients and pKa values (57). Therefore, stereoselective active renal secretion may be the mechanism responsible for the observed differences in the renal clearances of quinine and quinidine. 

Bocci V, Pacini A, Muscettola M, Paulesu L, Pessina GP, santiano M, Viano Al. Renal filtration, absorption and catabolism of human alpha interferon. J Interferon Res, 1981,3 347-352... 

Pharmacokinetics All oral H -receptor antagonists are rapidly absorbed within 1 to 3 hours. Oral bioavailability is lower for ranitidine, cimetidine, and famotidine than for nizatidine. This is because ranitidine, cimetidine, and famotidine are incompletely absorbed and undergo first-pass hepatic metabolism. All of the Hj-receptor antagonists are eliminated via renal filtration and secretion. For this reason, the Hj-receptor antagonist T A may be increased in patients with renal dysfunction. 

Creatinine, an endogenous end product of muscle metabolism, is often measured in plasma and urine to determine creatinine clearance. Since, creatinine is freely filtered at the glomerulus and is not reabsorbed or secreted by the proximal tubule of most species, creatinine clearance provides a good measure of the GFR. Another endogenous compound, urea, is also cleared mainly by renal filtration and excretion. Increases in the blood or serum concentration of urea are indicative of decreased GFR. However, increases in BUN concentration occur only after substantial renal damage has been established. Thus, BUN concentration is not a sensitive indicator of nephrotoxicity and changes usually occur later than changes in other parameters (e.g., enzymuria). 

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