Excretion organic anions

Rabbits form bicarbonate in the gut and absorb it. They do not have to form new bicarbonate in the kidneys and need not excrete ammonium ions in the urine, but they still need to excrete organic anions. These organic anions are accompanied in the urine by sodium or potassium ions, which can generate a severe negative sodium balance for the period that the rabbits are on a browse diet(Iason and Palo, 1991). Therefore, lagomorphs excrete biotransformational... 

Ni inuma, K., Nishigaki, R., Sugiyama Y., Biliary excretion of pravastatin in rats contribution of the excretion pathway mediated by canalicular multispecific organic anion transporter, Drug Metab. Dispos. 1997, 25, 1123-1129. 

Y. Sakurai, H. Motohashi, H. Ueo, S. Masuda, H. Saito, M. Okuda, N. Mori, M. Matsuura, T. Doi, A. Fukatsu, O. Ogawa, and K. Inui. Expression levels of renal organic anion transporters (OATs) and their correlation with anionic drug excretion in patients with renal diseases. Pharm Res 21 61-67 (2004). 

Kirk GJD, Santos EE, Santos MB. 1999. Phosphate solubilization by organic anion excretion from rice growing in aerobic soil rates of excretion and decomposition, effects on... 

Sugiyama, Y., Kato, Y., and Chu, X. (1998) Multiplicity of bdiary excretion mechanisms for the camptothecin derivative irinotecan (CPT-11), its metabolite SN-38, and its glucuronide role of canalicular multispecific organic anion transporter and P-glycoprotein. Cancer Chemother. Pharmacol. 42(suppl), S44-S49. 

Grantham JJ and Chonko AM. Renal handling of organic anions and cations Excretion of uric acid. In Brenner BM and Rector FC (eds.).7 The Kidney (4th ed). Philadelphia Saunders, 1991. 

Urate excretion is subject to modification by a variety of organic anions, including uricosuric agents. 

Tubular secretion The active secretory systems can rapidly remove the protein-bound drugs from the blood and transport them into tubular fluid as the drugs that are bound to proteins are not readily available for excretion by filtration. The drugs known to be secreted by organic anion secretory system (i.e. strong acids) are salicylates, chlorothiazide, probenecid, penicillin etc. and cation (i.e. bases) includes catecholamines, choline, histamine, hexamethonium, morphine etc. 

Certain molecules, such as p-aminohippuric acid (Fig. 3.18), a metabolite of p-aminobenzoic acid are actively transported from the bloodstream into the tubules by a specific anion transport system. Organic anions and cations appear to be transported by separate transport systems located on the proximal convoluted tubule. Active transport is an energy-requiring process and therefore may be inhibited by metabolic inhibitors, and there may be competitive inhibition between endogenous and foreign compounds. For example, the competitive inhibition of the active excretion of uric acid by compounds such as probenecid may precipitate gout. 

Membrane transporter proteins (MDR or ABC transporter proteins) such as p-glycoprotein are crucially important in the process of excretion and also in absorption and distribution and elimination of chemicals from cells. These transport organic anions or cations and neutral compounds across membranes, pump unwanted chemicals out of cells such as in gut, placenta, and brain, transport chemicals into bile from liver cells, and facilitate excretion from the kidney. 

Although bile acid conjugates with amino acids are normally excreted into bile, amino acid conjugates of xenobiotics are usually excreted into urine. Conjugation with endogenous amino acids facilitates urinary excretion because of the organic anion transport systems located in the kidney tubules. 

Mycophenolate mofetil is rapidly absorbed after oral administration, and the bioavailability of its oral dose is 94%. It is metabolized by esterases to free MPA, which is the active metabolite. The enterohepatic recirculation plays a crucial role in the serum levels of MPA. The active metabolite is further metabolized by glucuronyl transferase and is eliminated (90%) in urine as the MPA glucuronide (MPAG) as a result of the organic anion transport system in the proximal tubule. A small amount is excreted in feces. 

The pH-buffering of extracellular fluid depends in part on the carbon dioxide/ bicarbonate equilibrium so that the intake of sodium bicarbonate is followed by a brief alkalosis and an increased excretion of sodium carbonate in the urine. Depending on its carbonate concentration, the pH of the urine may rise to 8.07. Large doses (80—100 g/day) of sodium bicarbonate were needed if the pH of stomach contents was to be maintained at 4 or over in patients with duodenal ulcers8. Oxidation of organic anions in the body to carbon dioxide and water permits the use of sodium citrate, lactate or tartrate instead of sodium bicarbonate. In an analogous manner the ingestion of ammonium chloride induces a brief acidosis as a result of the metabolic conversion of ammonia to urea and lowers the pH of the urine. 

Schaub et al. demonstrated that Mrp2/MRP2 is expressed in the proximal tubules in the kidney (241,242). In vivo study and clinical study supports that Mrp2/MRP2 is involved in the tubular secretion of organic anions. The urinary excretion rates of calcein and fluo-3 were three to four times lower in perfused kidneys from TR rats compared with normal rats, and the renal excretion of lucifer yellow was delayed in TR rats (243). Hulot et al. identified a heterozygous mutation, which results in a loss of function of MRP2, in the patient who showed delay of renal MTX elimination (244). 

Kato Y, Kuge K, Kusuhara H, et al. Gender difference in the urinary excretion of organic anions in rats. J Pharmacol Exp Ther 2002 302 483 189. 

Kusuhara H, Suzuki H, Sugiyama Y. The role of P-glycoprotein and canalicular multi specific organic anion transporter in the hepatobiliary excretion of chugs. J Pharm Sci 1998 87 1025-1040. 

Masuda M, I lzuka Y, Yamazaki M, et al. Methotrexate is excreted into the bile by canalicular multispecific organic anion transporter in rats. Cancer Res 1997 57 (16) 3506-3510. 

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