Excretion organic anion transporters

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). 

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. 

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. 

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. 

Figure 28.3. Transport of bile acids and other constituents across the hepatocyte. The Na+ dependent bile salt (taurocholate) transporter (BA-) is shown on the sinusoidal membrane that utihzes the Na+ gradient maintained by the NAK pump, shown here on the lateral aspect of the plasmalemma. Bile salt transcellular transport involves microtubules, which then dehver substrate to the canahcular bile salt transporter (1). Bilary excretion of GSH, gluc-uronate (GluA), and sulfate conjugates of compounds such as 17P-estradiol (E2), bilirubin, and bromosulfothalein (BSP) is catalyzed by the multispecific organic anion transporter (MOAT 2). Both 1 and 2 are members of the ABC family of ATP-dependent transporters that also includes P-glycoprotein (3), another canalicular transporter catalyzing excretion of hpophihc compounds such as the chemotherapeutic drug, daunorubicin.

TENOFOVIR ADEFOVIR, CIDOFOVIR t adverse effects T plasma levels, competition for renal excretion via organic anion transporter Monitor renal function weekly... 

Both irinotecan and SN-38 are primarily excreted into the bile by the canalicular multispecific organic anion transporter (cMOAT), a member of the ATP cassette of transporters. Therefore, inhibitors of cMOAT, such as ciclosporin, can reduce the clearance of irinotecan and SN-38 (41,42). 

K. I., Hakusui, H. and Sugiyama, Y. (1997) Multispedfic organic anion transporter is responsible for the biliary excretion of the camptothedn derivative irinotecan and its metabolites in rats. The Journal of Pharmacology and Experimental Therapeutics, 281, 304—314. 

Robertson EE, Rankin GO (2006) Human renal organic anion transporters characteristics and contributions to drug and drug metabolite excretion. Pharmacol Ther 109(3) 399-412... 

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