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Renal handling of drugs and xenobiotics

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Clinical Nephrotoxins

Pharmacology and clinical pharmacology define the desirable and undesirable effects of drugs and xenobiotics whereas pharmacokinetics defines the various processes that are involved in absorption - distribution - elimination of these agents. Needless to say that the former may strongly influence the latter.

The kidney and the liver have complementary functions in the elimination of drugs and xenobiotics. Lipophilic non-ionic substances of molecular weight higher than 300-500 dalton and highly bound to proteins appear to be eliminated by the liver, while the kidney prefers hydrophilic substances of molecular weight smaller than approximately 500 daltons. Metabolism occurs predominantly in the liver, transforming the original substance into more polar and more hydrophilic metabolites, which became dependent on the kidney for elimination. Consequently, the majority of all drugs and xenobiotics in one way or another have to pass through the kidney. In addition to this important “gateway” function of substances, which are not always without side-effects, the kidney itself is particularly sensitive to drugs and xenobiotics.

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References

  1. Brezis M, Rosen S, Silva P, Epstein FH. Renal ischemia: a new perspective. Kidney Int 1984; 26: 374-383.

    Google Scholar 

  2. Rush GF, Smith JH, Newton JF, Hook JB. Chemically induced nephrotoxicity: role of metabolic activation. CRC Crit Rev Toxicol 1984; 13: 99-160.

    Google Scholar 

  3. Hook JB, Hewitt WR. Toxic responses of the kidney. In: Casarett & Doull’s Toxicology. The basic science of poisons, 3rd edition. Klaassen CD, Amdur MO, Doull J (editors). Macmillan, New York 1986; p. 310-329.

    Google Scholar 

  4. Tay LK, Bregman CL, Masters BG, Williams PD. Effects of cis-diamminedi chloro plati num (II) on rabbit kidney in vivo and on rabbit renal proximal tubule cells in culture. Cancer Res 1988; 48: 2538-2543.

    PubMed  Google Scholar 

  5. Williams PD. The application of renal cells in culture in studying drug-induced nephrotoxicity. In vitro 1989; 25: 800-805.

    Google Scholar 

  6. Williams PD, Rush GF. An evaluation of in vitro models for assessing nephrotoxicity. In: In vitro toxicity testing. Frazier JM (editor). Marcel Dekker Inc, New York/Basel/Hong Kong 1992; p. 85-110.

    Google Scholar 

  7. Kastner S, Soose M, Stolte H. Human kidney in in vitro pharmaco-toxicology. In: Human cells in in vitro pharmaco-toxicology: present status within Europe. Rogiers V, Sonck W, Shephard E, Vercruysse A (editors). VUBPress, Brussels 1993; p. 197-238.

    Google Scholar 

  8. Brater DC, Sokal PP, Hall SD, McKinney TD. Disposition and dose require ments of drugs in renal insufficiency. In: The kidney: physiol ogy and pathophysiology. Seldin DW, Giebisch G (editors). Raven Press Ltd, New York 1992; p. 3671-3695.

    Google Scholar 

  9. Hörbelt M, Wotzlaw C, Sutton TA, Molitoris BA, Philipp T, Kribben A, Fandrey J, Pietruck F, Pietruck F. Organic cation transport in the rat kidney in vivo visualized by time-resolved two-photon microscopy. Kidney Int 2007; 72: 422-429.

    PubMed  Google Scholar 

  10. Koepsell H, Koepsell H. In vivo two-photon fluorescence microscopy opens a new area for investigation of the excretion of cationic drugs in the kidney. Kidney Int 2007; 72: 387-388.

    PubMed  Google Scholar 

  11. John EG & Guignard JP. Development of renal excretion of drugs during ontogeny. In: Neonatal and fetal medicine. Polin RA & Fow WW Eds. Saunders WB, Philadelphia. pp 188-193, 1997.

    Google Scholar 

  12. Kragh-Hansen U. Molecular aspects of ligand binding to serum albumin. Pharmacol Rev 1981; 33: 17-53.

    PubMed  Google Scholar 

  13. Routledge PA. The plasma protein binding of basic drugs. Brit J Clin Pharmacol 1986; 22: 499-506.

    Google Scholar 

  14. Green TP, Mirkin BL. Resistance of proteinuric rats to furosemide: urinary drug protein bindings as a determinant of drug effect. Life Sci 1980; 26: 623-630.

    PubMed  Google Scholar 

  15. Green TP, Mirkin BL. Furosemide disposition in normal and proteinuric rats: urinary drug protein bindings as a determinant of drug excretion. J Pharmacol Exp Ther 1981; 218: 122-127.

    PubMed  Google Scholar 

  16. Kirchner KA, Voelker JR, Brater DC. Intratubular albumin blunts the response to furosemide - a mechanism for diuretic resistance in the nephrotic syndrome. J Pharmacol Exp Ther 1990; 252: 1097-101.

    PubMed  Google Scholar 

  17. Kirchner KA, Voelker JR, Brater DC. Binding inhibitors restore furosemide potency in tubule fluid containing albumin. Kidney Int 1991; 40: 418-424.

    PubMed  Google Scholar 

  18. Weiner IM. Organic acids and bases and uric acid. The kidney: physiology and pathophysiology. Seldin DW, Giebisch G (editors). Raven Press Ltd, New York 1985; p. 1703-1724.

    Google Scholar 

  19. Roch-Ramel F, Roth L, Arnow J, Weiner LM. Salicylate excretion in the rat; free flow micropuncture experiments. J Pharmacol Exp Ther 1978; 207: 737-747.

    PubMed  Google Scholar 

  20. Brater DC. Drugs and the kidney: renal contribution to handling of drugs. In: Handbook of renal therapeutics. Martínez-Maldonado M (editor). Plenum Medical Book Company, New York/London 1983; p. 191-206.

    Google Scholar 

  21. Goodman LS, Gilman A, Rall TW, Nies AS, Taylor P (editors). The pharmacol ogi cal basis of therapeutics. Pergamon Press, New York 1990.

    Google Scholar 

  22. Roch-Ramel F, Besseghir K, Murer H. Renal excretion and tubular transport of organic anions and cations. In: Handbook of physiology, section 8: renal physiology. Windhager EE (editor). Oxford University Press, New York/Oxford 1992; p. 2189-2262.

    Google Scholar 

  23. Guggino SE, Aronson PS. Paradoxical effects of pyrazinoate and nicotinate on urate transport in dog renal microvillus membranes. J Clin Invest 1985; 76: 543-547.

    PubMed  Google Scholar 

  24. Bessighir K, Roch-Ramel F. Pyrazinoate transport in the isolated perfused rabbit proximal tubule. Pflügers Arch 1986; 407: 643-648.

    Google Scholar 

  25. Elion GB, Yü TF, Hitchings GH. Renal clearance of oxipurinol, the chief metabolite of allopurinol. Am J Med 1968; 45: 69-77.

    PubMed  Google Scholar 

  26. May DG, Weiner IM. The renal mechanisms for the excretion of m-hydroxyben zoic acid in cebus monkeys: relationship to urate transport. J Pharmacol Exp Ther 1971; 176: 407-417.

    PubMed  Google Scholar 

  27. Van Crugten JT, Sallustio BC, Nation RL, Somogyi A. Renal tubular transport of mor phine, morphine-6-glucuronide, and morphine-3-glucuronide in the isolated perfused rat kidney. Drug Metab Disp 1991; 19: 1087-1092.

    Google Scholar 

  28. Wright SH, Wunz TM, Wunz TP. A choline transporter in renal brush-border membrane vesicles - energetics and structural specificity. J Membrane Biol 1992; 126: 51-65.

    Google Scholar 

  29. Daniel H, Herget M. Cellular and molecular mechanisms of renal peptide transport. (review). Am J Physiol 1997; 273: F1-F8.

    PubMed  Google Scholar 

  30. Shen H, Smith DE, Yang T, Huang YG, Schnermann JB, Brosius FCI. Localization of PEPT1 nand PEPT2 proton-coupled oligopeptide cotransporter mRNA and protein in rat kidney. Am J Physiol 1999; 276: F658-F665.

    PubMed  Google Scholar 

  31. Keppler D, Leier I, Jedlitschky G. Transport of glutathione conjugates and glucuronides by the multidrug resistance proteins MRP1 and MRP2 (review). Biol Chem 1997; 378: 787-791.

    PubMed  Google Scholar 

  32. Inui K, Masuda S, Saito H. Cellular and molecular aspects of drug transport in the kidney. Kidney Int 2000; 58: 944-958.

    PubMed  Google Scholar 

  33. Foulkes EC. Transport of heavy metals by the kidney. Toxicology Letters 1990; 33: 29-31.

    Google Scholar 

  34. Templeton DM. Cadmium uptake by cells of renal origin. J Biol Chem 1990; 265: 21764-21770.

    PubMed  Google Scholar 

  35. De Broe ME, Paulus GJ, Verpooten GA, Roels F, Buyssens N, Wedeen RP, Van Hoof F, Tulkens PM. Early effects of gentamicin, tobramycin and amikacin on the human kidney. A prospective, comparative study. Kidney Int 1984; 25: 643-652.

    PubMed  Google Scholar 

  36. Laurent G, Tulkens PM. Aminoglycoside nephrotoxicity: cellular and molecular aspects. ISI Atlas of Science - Pharmacology 1987; 1: 40-44.

    Google Scholar 

  37. Lee W and Kim RB. Transporters and renal drug elimination. Annu Rev Pharmacol Toxicol 2004; 44: 137-66.

    PubMed  Google Scholar 

  38. Besseghir K, Roch-Ramel F. Renal excretion of drugs and other xenobiotics. Renal Physiol 1987; 10: 221-241.

    PubMed  Google Scholar 

  39. Dresser, M. J., Leabman, M. K., and Giacomini, K. M. Transporters involved in the elimination of drugs in the kidney: Organic anion transporters and organic cation transporters [Review]. Journal of Pharmaceutical Sciences 90(4), 397-421. 2001.

    PubMed  Google Scholar 

  40. Berkhin, E. B. and Humphreys, M. H. Regulation of renal tubular secretion of organic compounds [Review]. Kidney International 59, 17-30. 2001.

    PubMed  Google Scholar 

  41. Møller JV, Sheikh MI. Renal organic anion transport system: pharmacological, physio logical, and biochemical aspects. Pharmacol Rev 1983; 34: 315-358.

    Google Scholar 

  42. Ullrich KJ. Specificity of transporters for organic anions and organic cations in the kidney. Biochim Biophys Acta 1994; 1197: 45-62.

    PubMed  Google Scholar 

  43. Burckhardt G, Wolff NA. Structure of renal organic anion and cation transporters (review). Am J Physiol Renal Physiol 2000; 278(6): F853-F866

    PubMed  Google Scholar 

  44. Sekine T, Cha SH, Endou H. The multispecific organic anion transporter (OAT ) family (review). Pflügers Arch 2000; 440(3): 337-350.

    PubMed  Google Scholar 

  45. Tune BM. Renal tubular transport and nephrotoxicity of β-lactam antibiotics: struc ture-activity relationships. Miner Electrolyte Metab 1994; 20: 221-231.

    PubMed  Google Scholar 

  46. Dantzler WH, Evans KK, Groves CE, Welborn JR, North J, Stevens JL, Wright SH. Relation of cysteine conjugate nephrotoxicity to transport by the basolateral organic anion transport system in isolated S2 segments of rabbit proximal renal tubules. J Pharm Exp Ther 1998; 286: 52-60.

    Google Scholar 

  47. Berndt WO. The role of transport in chemical nephrotoxicity (review). Tox Pathol 1998; 26: 52-57.

    Google Scholar 

  48. Kosoglou T, Vlasses PH. Drug interactions involving renal transport mechanisms: an overview. CICP Ann Pharmacother 1989; 23: 116-22.

    Google Scholar 

  49. Pritchard JB, Miller DS. Mechanisms mediating renal secretion of organic anions and cations. Physiol Rev 1993; 73: 765-796.

    PubMed  Google Scholar 

  50. Roch-Ramel F. Renal transport of organic anions (review). Curr Opin Nephrol Hypertens 1998; 7(5): 517-524.

    PubMed  Google Scholar 

  51. Karniski LP, Lotscher M, Fucentese M, Hilfiker H, Biber J, Murer H. Immunolocalization of sat-1 sulfate/oxalate/bicarbonate anion exchanger in the rat kidney. Am J Physiol 1998; 275(1 Pt 2): F79-F87.

    PubMed  Google Scholar 

  52. Wang H, Fei YJ, Kekuda R, Yang-Feng TL, Devoe D, Leibach FH, Prasad PD, Ganapathy V. Structure, function, and genomic organization of human Na+-dependent high-affinity dicarboxylate transporter. Am J Physiol 2000; 278: C1019-C1030.

    Google Scholar 

  53. Klein I, Sarkadi B, Varadi A. An inventory of the human ABC proteins (review). Biochim Biophys Acta 1999; 1461: 237-262.

    PubMed  Google Scholar 

  54. Borst P, Evers R, Kool M, Wijnholds J. A family of drug transporters: the multidrug resistance-associated proteins (review). J Nat Cancer Inst 2000; 92: 1295-1302.

    PubMed  Google Scholar 

  55. Masuda S, Terada T, Yonezawa A, Tanihara Y, Kishimoto K, Katsura T, Ogawa O, and Inui K. Identification and functional characterization of a new human kidney-specific H+/organic cation antiporter, kidney-specific multidrug and toxin extrusion 2. J Am Soc Nephrol 2006; 17: 2127-2135.

    PubMed  Google Scholar 

  56. Omote H, Hlasa M, Matsumo T et al. The MATE proteins as fundamental transporters of metabolic and xenobiotic organic cations. Trends Pharmacol Sci 2006; 27: 587-593.

    PubMed  Google Scholar 

  57. Lu R, Kanai N, Bao Y, Wolkoff AW, Schuster VL. Regulation of renal OATP mrna expression by testosterone. Am J Physiol 1996; 270(2 Pt 2): F332-F337.

    PubMed  Google Scholar 

  58. Masuda S, Ibaramoto K, Takeuchi A, Saito H, Hashimoto Y, Inui KI. Cloning and functional characterization of a new multispecific organic anion transporter, OAT-K2, in rat kidney. Mol Pharmacol. 1999; 55(4): 743-752

    PubMed  Google Scholar 

  59. Masuda S, Takeuchi A, Saito H, Hashimoto Y, Inui K. Functional analysis of rat renal organic anion transporter OAT-K1: bidirectional methotrexate transport in apical membrane. FEBS Letters 1999; 459: 128-132.

    PubMed  Google Scholar 

  60. Eraly SA, Blantz RC, Bhatnagar V, Nigam SK. Novel aspects of renal organic anion transporters. Curr Opin Nephrol Hypertens 2003; 12: 551-558.

    PubMed  Google Scholar 

  61. Yabuuchi H, Tamai I, Nezu J, Sakamoto K, Oku A, Shimane M, Sai Y, Tsuji A. Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. J Pharmacol Exp Ther 1999; 289: 768-773.

    PubMed  Google Scholar 

  62. Wu X, Huang W, Prasad PD, Seth P, Rajan DP, Leibach FH, Chen JW, Conway SJ, Ganapathy V. Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter. J Pharmacol Exp Ther 1999; 290: 1482-1492.

    PubMed  Google Scholar 

  63. Huls M, Brown CD, Windass AS, Sayer R, van den Heuvel JJ, Heemskerk S, Russel FG, Masereeuw R. The breast cancer resistance protein transporter ABCG2 is expressed in the human kidney proximal tubule apical membrane. Kidney Int 2007; 73: 220-225.

    PubMed  Google Scholar 

  64. Miller DS, Stewart DE, Pritchard JB. Intracellular compartmentation of organic anions within renal cells. Am J Physiol 1993; 264: R882-R890.

    PubMed  Google Scholar 

  65. Masereeuw R, vandenBergh EJ, Bindels RJ. Characterization of fluorescein transport in isolated proximal tubular cells of the rat: evidence for mitochondrial accumul ation. J Pharmacol Exp Ther 1994; 269: 1261-1267.

    PubMed  Google Scholar 

  66. Pajor AM. Sequence and functional characterization of a renal sodium/dicarboxylate cotransporter. J Biol Chem 1995; 270(11): 5779-5785.

    PubMed  Google Scholar 

  67. Lemieux G, Junco E, Perez R, Lemieux C, Allignet E. The metabolic response of the kidney to acute sodium lactate alkalosis. Can J Physiol Pharmacol 1985; 63: 687-692.

    PubMed  Google Scholar 

  68. Miller DS, Barnes DM, Pritchard JB. Confocal microscopic analysis of fluores cein compartmentation within crab urinary bladder cells. Am J Physiol 1994; 267: R16-R25.

    PubMed  Google Scholar 

  69. Miller DS, Pritchard JB. Nocodazole inhibition of organic anion secretion in teleost renal proximal tubules. Am J Physiol 1994; 267: R695-R704.

    PubMed  Google Scholar 

  70. Ullrich KJ, Rumrich G. Luminal transport step of para-aminohippurate (PAH) - transport from pah-loaded proximal tubular cells into the tubular lumen of the rat kidney in vivo. Pflügers Arch 1997; 433(6): 735-743

    PubMed  Google Scholar 

  71. Roch-Ramel F, Werner D, Guisan B. Urate transport in brush-border membrane of human kidney. Am J Physiol 1994; 266: F797-F805.

    PubMed  Google Scholar 

  72. Roch-Ramel F, Guisan B, Schild L. Indirect coupling of urate and p-aminohippurate transport to sodium in human brush-border membrane vesicles. Am J Physiol 1996; 270: F165-F272.

    Google Scholar 

  73. Schmitt C, Burckhardt G. p-Aminohippurate/2-oxoglutarate exchange in bovine renal brush-border and basolateral membrane vesicles. Pflügers Arch 1993; 423: 280-290.

    PubMed  Google Scholar 

  74. Ullrich KJ, Rumrich G. Renal contraluminal transport systems for organic anions (p-aminohippurate, p-aminohip purate) and organic cations (N1-methyl-nicotinamide, NMeN) do not see the degree of substrate ionization. Pflügers Arch 1992; 421: 286-288.

    PubMed  Google Scholar 

  75. Troehler U, Bonjour JP, Fleisch H. Renal secretion of diphosphonates in rats. Kidney Int 1975; 8: 6-13.

    PubMed  Google Scholar 

  76. Lin JH, Chen IW, Deluna FA, Hichens M. Renal handling of alendronate in rats. An uncharac terized renal transport system. Drug Metab Dispos 1992; 20: 608-613.

    PubMed  Google Scholar 

  77. Russel FGM, Vermeulen WG. Effect of substituted benzoylglycines (hippurates) and phenylacetylglycines on p-aminohippurate transport in dog renal membrane vesicles. Pharmaceut Res 1994; 11: 1829-1833.

    Google Scholar 

  78. Russel FGM, Heijn M, De Laet RC, Van Ginneken CAM. Effect of substituted benzoates on p-aminohip purate transport in dog renal membrane vesicles. Nau nyn-Schmiedeberg’s Arch Pharma col 1991; 343: 102-107.

    Google Scholar 

  79. Hosoyamada M, Sekine T, Kanai Y, Endou H. Molecular cloning and functional expression of a multispecific organic anion transporter from human kidney. Am J Physiol 1999; 276: F122-F128.

    PubMed  Google Scholar 

  80. Van Aubel RAMH, Masereeuw R, Russel FGM. Molecular pharmacology of renal organic anion transporters (review). Am J Physiol Renal Physiol 2000; 279(2): F216-F232.

    PubMed  Google Scholar 

  81. Uwai Y, Saito H, Hashimoto Y, Inui KI. Interaction and transport of thiazide diuretics, loop diuretics, and acetazolamide via rat renal organic anion transporter rOAT1. J Pharmacol Exp Ther 2000; 295: 261-265.

    PubMed  Google Scholar 

  82. Wada S, Tsuda M, Sekine T, Cha SH, Kimura M, Kanai Y, Endou H. Rat multispecific organic anion transporter 1 (rOAT1) transports zidovudine, acyclovir, and other antiviral nucleoside analogs. J Pharmacol Exp Ther 2000; 294: 844-849.

    PubMed  Google Scholar 

  83. Cihlar T, Lin DC, Pritchard JB, Fuller MD, Mendel DB, Sweet DH. The antiviral nucleotide analogs cidofovir and adefovir are novel substrates for human and rat renal organic anion transporter 1. Mol Pharmacol 1999; 56: 570-580.

    PubMed  Google Scholar 

  84. Sekine T, Watanabe N, Hosoyamada M, Kanai Y, Endou H. Expression cloning and characterization of a novel multispecific organic anion transporter. J Biol Chem 1997; 272: 18526-18529.

    PubMed  Google Scholar 

  85. Burckhardt BC, Wolff NA, Burckhardt G. Electrophysiologic characterization of an organic anion transporter cloned from winter flounder kidney (fROAT ). J Am Soc Nephrol 2000; 11(1): 9-17.

    PubMed  Google Scholar 

  86. Race J E, Grassl SM, Williams WJ, Holtzman EJ. Molecular cloning and characterization of two novel human renal organic anion transporters (hOAT1 and hOAT3). Biochem Biophys Res Comm 1999; 255: 508-514.

    PubMed  Google Scholar 

  87. Boner G, Steele TH. Relationship of urate and p-aminohippurate secretion in man. Am J Physiol 19973; 225: 100-104.

    Google Scholar 

  88. Uwai Y, Okuda M, Takami K, Hashimoto Y, Inui K. Functional characterization of the rat multispecific organic anion transporter OAT1 mediating basolateral uptake of anionic drugs in the kidney. FEBS Letters 1998; 438: 321-324.

    PubMed  Google Scholar 

  89. Lu R, Chan BS, Schuster VL. Cloning of the human kidney PAH transporter: narrow substrate specificity and regulation by protein kinase C. Am J Physiol 1999; 276: F295-303.

    PubMed  Google Scholar 

  90. Cha, S. H., Sekine, T., Fukushima, J., Kanai, Y., Kobayashi, Y., Goya, T., and Endou, H. Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Molecular Pharmacology 59(5), 1277-1286. 2001.

    PubMed  Google Scholar 

  91. Sekine T, Cha S, Kanai Y, Endou H. Molecular biology of multispecific organic anion transporter family (OAT family). Clin Exp Nephrol 1999; 3: 237-243.

    Google Scholar 

  92. Kusuhara H, Sekine T, Utsunomiya-Tate N, Tsuda M, Kojima R, Cha SH, Sugiyama Y, Kanai Y, Endou H. Molecular cloning and characterization of a new multispecific organic action transporter from rat brain. J Biol Chem 1999; 274: 13675-13680.

    PubMed  Google Scholar 

  93. Nakajima N, Sekine T, Cha SH, Tojo A, Hosoyamada M, Kanai Y, Yan K, Awa S, Endou H. Developmental changes in multispecific organic anion transporter 1 expression in the rat kidney. Kidney Int 2000; 57: 1608-1616.

    PubMed  Google Scholar 

  94. Uchino H, Tamai I, Yamashita K, Minemoto Y, Sai Y, Yabuuchi H, Miyamoto K, Takeda E, Tsuji A. p-aminohippuric acid transport at renal apical membrane mediated by human inorganic phosphate transporter NPT1. Biochem Biophys Res Comm 2000; 270: 254-259.

    PubMed  Google Scholar 

  95. Busch AE, Schuster A, Waldegger S, Wagner CA, Zempel G, Broer S, Biber J, Murer H, Lang F. Expression of a renal type I sodium/ phosphate transporter (NaPi-1) induces a conductance in Xenopus oocytes permeable for organic and inorganic anions. Proc Natl Acad Sci USA 1996; 93(11): 5347-5351.

    PubMed  Google Scholar 

  96. Schaub TP, Kartenbeck J, Konig J, Spring H, Dorsam J, Staehler G, Storkel S, Thon WF, Keppler D. Expression of the MRP2 geneencoded conjugate export pump in human kidney proximal tubules and in renal cell carcinoma. J Am Soc Nephrol 1999; 10: 1159-1169.

    PubMed  Google Scholar 

  97. Bakos E, Evers R, Sinko E, Varadi A, Borst P, Sarkadi B. Interactions of the human multidrug resistance proteins MRP1 and MRP2 with organic anions. Mol Pharmacol 2000; 57: 760-768.

    PubMed  Google Scholar 

  98. Leier I, Hummel-Eisenbeiss J, Cui YH, Keppler D. ATP-dependent para-aminohippurate transport by apical multidrug resistance protein MRP2. Kidney Int 2000; 57: 1636-1642.

    PubMed  Google Scholar 

  99. Van Aubel RAMH, Peters JGP, Masereeuw R, van Os CH, Russel FGM. Multidrug resistance protein Mrp2 mediates ATP-dependent transport of classic renal organic anion p-aminohippurate. Am J Physiol Renal Physiol 2000; 279(4): F713-F717.

    PubMed  Google Scholar 

  100. Peng KC, Cluzeaud F, Bens M, Van Huyen JP, Wioland MA, Lacave R, Vandewalle A. Tissue and cell distribution of the multidrug resistance-associated protein (MRP) in mouse intestine and kidney. J Histochem Cytochem 1999; 47: 757-768.

    PubMed  Google Scholar 

  101. Smeets PH, van Aubel RA, Wouterse AC, van den Heuvel JJ, and Russel FG. Contribution of multidrug resistance protein 2 (MRP2/ ABCC2) to the renal excretion of p-aminohippurate (PAH) and identification of MRP4 (ABCC4) as a novel PAH transporter. J Am Soc Nephrol 2004; 15: 2828-2835.

    PubMed  Google Scholar 

  102. Abe T, Kakyo M, Sakagami H, Tokui T, Nishio T, Tanemoto M, Nomura H, Hebert SC, Matsuno S, Kondo H, Yawo H. Molecular characterization and tissue distribution of a new organic anion transporter subtype (oatp3) that transports thyroid hormones and taurocholate and comparison with oatp2. J Biol Chem 1998; 273: 22395-22401.

    PubMed  Google Scholar 

  103. Masuda S, Saito H, Inui KI. Interactions of nonsteroidal anti-inflammatory drugs with rat renal organic anion transporter, OAT-K1. J Pharmacol Exp Ther 1997; 283: 1039-1042.

    PubMed  Google Scholar 

  104. Pritchard JB, Sykes DB, Walden R, Miller DS. ATP-dependent transport of tetraethylammonium by endosomes isolated from rat renal cortex. Am J Physiol 1994; 266: F966-F976.

    PubMed  Google Scholar 

  105. Dutt A, Heath LA, Nelson JA. P-glycoprotein and organic cation secretion by the mammalian kidney. J Pharmacol Exp Ther 1994; 269: 1254-1260.

    PubMed  Google Scholar 

  106. Ott RJ, Hui AC, Yuan G, Giacomini KM. Organic cation transport in human renal brush-border membrane vesicles. Am J Physiol 1991; 261: F443-F451.

    PubMed  Google Scholar 

  107. Takahashi Y, Itoh T, Kobayashi M, Sugawara M, Saitoh H, Iseki K, Miyazaki K, Miyazaki S, Takada M, Kawashima Y. The transport mechanism of an organic cation, disopyramide, by brush-border membranes: comparison between renal cortex and small intestine of the rat. J Pharm Pharmacol 1993; 45: 419-424.

    PubMed  Google Scholar 

  108. Wright SH, Wunz TM, Wunz TP. Structure and interaction of inhibitors with the tetraethylammonium/H+ exchanger of rabbit renal brush border membranes. Pflügers Arch 1992; 429: 313-324.

    Google Scholar 

  109. David C, Rumrich G, Ullrich KJ. Luminal transport system for H+/organic cations in the rat proximal tubule. Kinetics, dependence on pH; specificity as compared with the contraluminal organic cation-transport system. Pflüugers Arch 1995; 430(4): 477-492.

    Google Scholar 

  110. Wright S H, Wunz TM. Influence of substrate structure on turnover of the organic cation/H+ exchanger of the renal luminal membrane. Pflügers Arch 1998; 436: 469-477.

    PubMed  Google Scholar 

  111. Wright SH, Wunz TM. Influence of substrate structure on substrate binding to the renal organic cation H+ exchanger. Pflügers Arch 1999; 437: 603-610.

    PubMed  Google Scholar 

  112. Miyamoto Y, Tiruppathi C, Ganapathy V, Leibach FH. Multiple transport systems for organic cations in renal brush-border mem- branes vesicles. Am J Physiol 1989; 256: F540-F548.

    PubMed  Google Scholar 

  113. Ford JM, Hait WN. Pharmacology of drugs that alter multidrug resistance in cancer. Pharmacol Rev 1990; 42: 156-199.

    Google Scholar 

  114. Speeg KV, Maldonado AL, Liaci J, Muirhead D. Effect of cyclosporine on colchicine secretion by the kidney multidrug transporter studied in vivo. J Pharmacol Exp Ther 1992; 261: 50-55.

    PubMed  Google Scholar 

  115. De Lannoy IAM, Mandin RS, Silverman M. Renal secretion of vinblastine, vincristine and colchicine in vivo. J Pharmacol Exp Ther 1994; 268: 388-395.

    PubMed  Google Scholar 

  116. Schramm U, Fricker G, Wenger R, Miller DS. P-glycoprotein-mediated secretion of a fluorescent cyclosporin analogue by teleost renal proximal tubules. Am J Physiol 1995; 268: F46-F52.

    PubMed  Google Scholar 

  117. Horio M, Pastan I, Gottesma MM, Handler JS. Transepithelial transport of vinblastine by kidney-derived cell lines. Application of a new kinetic model to estimate in situ Km of the pump. Biochim Biophys Acta 1990; 1027: 116-122.

    PubMed  Google Scholar 

  118. Koren G. Clinical pharmacokinetic significance of the renal tubular secretion of digoxin. Clin Pharmacokin 1987; 13: 334-343.

    Google Scholar 

  119. Koziolek MJ, Riess R, Geiger H et al. Expression of multidrug resistance P-glycoprotein in kidney allografts from cyclosporine A-treated patients. Kidney Int 2001; 60: 156-166.

    PubMed  Google Scholar 

  120. Saeki T, Ueda K, Tanigawara Y et 01. Human P-glycoprotein transports cyclosporin A and FK506. J Biol Chem 1993; 268: 60776080.

    Google Scholar 

  121. Del Moral RG, Olrno A, Osuna A et a/. Role of P-glycoprotein in chronic cyclosporine nephrotoxicity and its relationship to intra- renal angiotensin II deposits. Transplant Proc 1998; 30: 2014-2016.

    PubMed  Google Scholar 

  122. Garcia del Moral R, O’Valle F, Andujar M et al. Relationship between P-glycoprotein expression and cyclosporin A in kidney. An immunohistological and cell culture study. Am J Path01 1995: 146: 398-408.

    Google Scholar 

  123. Hauser IA, Schaeffeler E, Gauer S et al. ABCBl genotype of the donor but not of the recipient is a major risk factor for cyclosporlne- related nephrotoxicity after renal transplantation. J Am Soc Nephrol 2005; 16: 1501-1511.

    PubMed  Google Scholar 

  124. Miller DS, Fricker G, Drewe J. P-Glycoprotein-mediated transport of a fluorescent rapamycin derivative in renal proximal tubule. J Pharmacol Exp Ther 1997; 282: 440-444.

    PubMed  Google Scholar 

  125. Kahan BD. Efficacy of sirolimus compared with azathioprine for reduction of acute renal allograft rejection: a randomised mul- ticentre study. The Rapamune US Study Group. Lancet 2000; 356: 194-202.

    PubMed  Google Scholar 

  126. Pallet N, Thervet E, Le Corre D et al. Rapamycin inhibits human renal epithelial cell proliferation: effect on cyclin D3 mRNA expres- sion and stability. Kidney Int 2005; 67: 2422-2433.

    PubMed  Google Scholar 

  127. Koepsell H, Gorboulev V, Arndt P. Molecular pharmacology of organic cation transporters in kidney (review). J Membr Biol 1999; 167: 103-117.

    PubMed  Google Scholar 

  128. Zhang L, Brett CM, Giacomini KM. Role of organic cation transporters in drug absorption and elimination (review). Annual Rev Pharmacol Toxicol 1998; 38: 431-460.

    Google Scholar 

  129. Grundemann D, Gorboulev V, Gambaryan S, Veyhl M, Koepsell H. Drug excretion mediated by a new prototype of polyspecific transporter. Nature 1994; 372: 549-552.

    PubMed  Google Scholar 

  130. Okuda M, Urakami Y, Saito H, Inui K. Molecular mechanisms of organic cation transport in OCT2-expressing Xenopus oocytes. Biochim Biophys Acta 1999; 1417: 224-231.

    PubMed  Google Scholar 

  131. Zhang L, Gorset W, Washington CB, Blaschke TF, Kroetz DL, Giacomini KM. Interactions of HIV protease inhibitors with a human organic cation transporter in a mammalian expression system. Drug Metab Dispos 2000; 28: 329-334.

    PubMed  Google Scholar 

  132. Dresser MJ, Gray AT, Giacomini KM. Kinetic and selectivity differences between rodent, rabbit, and human organic cation trans- porters (OCT1). J Pharmacol Exp Ther 2000; 292: 1146-1152.

    PubMed  Google Scholar 

  133. Karbach U, Kricke J, Meyer-Wentrup F, Gorboulev V, Volk C, Loffing-Cueni D, Kaissling B, Bachmann S, Koepsell H. Localization of organic cation transporters OCT1 and OCT2 in rat kidney. Am J Physiol Renal Physiol 2000; 279(4): F679-F687.

    PubMed  Google Scholar 

  134. Sugawara-Yokoo M, Urakami Y, Koyama H, Fujikura K, Masuda S, Saito H, Naruse T, Inui K, Takata K. Differential localization of organic cation transporters rOCT1 and rOCT2 in the basolateral membrane of rat kidney proximal tubules. Histochem Cell Biol 2000; 114: 175-180.

    PubMed  Google Scholar 

  135. Urakami Y, Nakamura N, Takahashi K, Okuda M, Saito H, Hashimoto Y, Inui K. Gender differences in expression of organic cation transporter OCT2 rat kidney. FEBS Letters 1999; 461: 339-342.

    PubMed  Google Scholar 

  136. Wu XA, Huang W, Ganapathy ME, Wang HP, Kekuda R, Conway SJ, Leibach FH, Ganapathy V. Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney. Am J Physiol Renal Physiol 2000; 279: F449-F458.

    PubMed  Google Scholar 

  137. Grundemann D, Liebich G, Kiefer N, Koster S, Schomig E. Selective substrates for non-neuronal monoamine transporters. Mol Pharmacol 1999; 56(1): 1-10.

    PubMed  Google Scholar 

  138. Tamai I, Yabuuchi H, Nezu J, Sai Y, Oku A, Shimane M, Tsuji A. Cloning and characterization of a novel human ph-dependent organic cation transporter, OCTN1. FEBS Letters 1997; 419: 107-111.

    Google Scholar 

  139. Ganapathy ME, Huang W, Rajan DP, Carter AL, Sugawara M, Iseki K, Leibach FH, Ganapathy V. β-lactam antibiotics as substrates for OCTN2, an organic cation/carnitine transporter. J Biol Chem 2000; 275: 1699-1707.

    PubMed  Google Scholar 

  140. Lang F. Regulating renal drug elimination? J Am Soc Nephrol 2005; 16: 1535-1536.

    PubMed  Google Scholar 

  141. Zaman GJ, Versantvoort CH, Smit JJ, et al. Analysis of the expression of MRP, the gene for a new putative transmembrane drug transporter, in human multidrug resistant lung cancer cell lines. Cancer Res 1993; 53: 1747-1750.

    PubMed  Google Scholar 

  142. Wijnholds J, Scheffer GJ, van der Valk M, van der Valk P, Beijnen JH, Scheper RJ, Borst P. Multidrug resistance protein I protects the oropharyngeal mucosal layer and the testicular tubules against drug-induced damage. J Exp Med 1998; 188: 797-808.

    PubMed  Google Scholar 

  143. Peng KC, Cluzeaud F, Bens M et al. Tissue and cell distribution of the multidrug resistance-associated protein (MRP) on mouse intestine and kidney. J Histochem Cytochem 1999; 47: 757-767.

    PubMed  Google Scholar 

  144. Schaub TP, Kartenbeck J, Konig J, Vogel O, Witzgall R, Kriz W, Keppler D. Expression of the conjugate export pump encoded by the mrp2 gene in the apical membrane of kidney proximal tubules. J Am Soc Nephrol 1997; 8: 1213-1221.

    PubMed  Google Scholar 

  145. Kool M, van der Linden M, de Haas M, et al. MRP3, an organic anion transporter able to transport anti-cancer drugs. Proc Natl Acad Sci USA 1999; 96: 6914-6919.

    PubMed  Google Scholar 

  146. Konig J, Rost D, Cui Y, Keppler D. Characterization of the human multidrug resistance protein isoform MRP3 localized to the basolateral hepatocyte membrance. Hepatology 1999; 29: 1156-1163.

    PubMed  Google Scholar 

  147. Wagner CA, Lukewille U, Kaltenbach S, Moschen I, Broer A, Risler T, Broer S, Lang F. Functional and pharmacological characteriza- tion of human Na+-carnitine cotransporter hOCTN2. Am J Physiol Renal Physiol 2000; 279: F584-F591.

    PubMed  Google Scholar 

  148. Seth P, Wu X, Huang W, Leibach FH, Ganapathy V. Mutations in novel organic cation transporter (OCTN2), an organic cation/car- nitine transporter, with differential effects on the organic cation transport function and the carnitine transport function. J Biol Chem 1999; 274: 33388-33392.

    PubMed  Google Scholar 

  149. Bowman RH. Renal secretion of [35S] furosemide and its depression by albumin binding. Am J Physiol 1975; 229: 93-98.

    PubMed  Google Scholar 

  150. Koschier FJ, Acara M. Transport of 2, 4, 5-trichlorophenoxyacetate in the isolated, perfused rat kidney. J Pharmacol Exp Ther 1979; 208: 287-293.

    PubMed  Google Scholar 

  151. Webb DE, Edwards RM, Grantham JJ. Dependence of proximal tubule p-amino hip purate secretion on serum proteins and meta- bolic substrates. Am J Physiol 1986; 251: F619-F626.

    PubMed  Google Scholar 

  152. Grantham JJ, Kennedy J, Cowley B. Tubule urate and p-aminohip purate trans port: sensitivity and specificity of serum protein inhibition. Am J Physiol 1987; 252: F683-F690.

    PubMed  Google Scholar 

  153. Rodrigues de Miranda JF, Hilbers CW. A nuclear magnetic resonance study of the kinetics of the binding of the renal contrast medium acetrizoate to albumin. Mol Pharmacol 1976; 12: 279-290.

    PubMed  Google Scholar 

  154. Ochwadt BK, Pitts RF. Disparity between phenol red and diodrast clearance in the dog. Am J Physiol 1956; 187: 318-322.

    PubMed  Google Scholar 

  155. Honari J, Blair AD, Cutler RE. Effects of probenecid on furosemide kinetics in man. Clin Pharmacol Ther 1977; 22: 395-401.

    PubMed  Google Scholar 

  156. Homeida M, Roberts C, Branch RA. Influence of probenecid and spironolactone on furosemide kinetics in man. Clin Pharmacol Ther 1977; 22: 402-409.

    PubMed  Google Scholar 

  157. Brater DC. Pharmacodynamic considerations in the use of diuretics. Annual Rev Pharmacol Toxicol 1983; 23: 45-62.

    Google Scholar 

  158. Li M, Anderson GD, Wang J. Drug-drug interactions involving membrane transporters in the human kideny. Expert Opin Drug Metab Toxicol 2006; 2: 505-532.

    PubMed  Google Scholar 

  159. Jacobs C, Kaubisch S, Halsey J, Lum BL, Gosland M, Coleman CN, Sikic BI. The use of probenecid as a chemoprotector against cisplatin nephrotoxicity. Cancer 1991; 67: 1518-1524.

    PubMed  Google Scholar 

  160. Ban M, Hettich D, Huguet N. Nephrotoxicity mechanism of cis-plantinum (II) diamine dichloride in mice. Toxicol Letters 1994; 71: 161-168.

    Google Scholar 

  161. Klein J, Bentur Y, Cheung D, Moselhy G, Koren G. Renal handling of cisplatin: interactions with organic anionas and cations in the dog. Clin Inv Med 1991; 14: 388-394.

    Google Scholar 

  162. Tracy TS, Krohn K, Jones DR, Bradly JD, Hall SD, Brates DC. The effects of a xalicylate, ibuprofen, and naproxen on the disposition in patients with rheumatoid arthritis. Eur J Clin Pharmacol 1992; 42: 121-125.

    PubMed  Google Scholar 

  163. Frenia ML, Long KS. Methotrexate and nonsteroidal antiinflammatory drug interac tions. Ann Pharmacother 1992; 26: 234-237.

    PubMed  Google Scholar 

  164. Nierenberg DW. Competitive inhibition of methotrexate accumulation in rabbit kidney slices by nonsteroidal anti-inflammatory drugs. J Pharmacol Exp Ther 1983; 226: 1-6.

    PubMed  Google Scholar 

  165. Fromm MF, Kim RB, Stein CM, Wilkinson GR, Roden DM. Inhibition of P-glycoprotein-mediated drug transport - A unifying mechanism to explain the interaction between digoxin and quinidine. Circulation 1999; 99: 552-557.

    PubMed  Google Scholar 

  166. Verschraagen M, Koks CHW, Schellens JHM, Beijnen JH. P-glycoprotein system as a determinant of drug interactions: the case of digoxin-verapamil. Pharmacol Res 1999; 40: 301-306.

    PubMed  Google Scholar 

  167. De Lannoy IAM, Koren G, Klein J, Charuk J, Silverman M. Cyclosporin and quinidine inhibition of renal digoxin excretion - evidence for luminal secretion of digoxin. Am J Physiol 1992; 263(4 Pt 2):F613-F622.

    PubMed  Google Scholar 

  168. De Lannoy IAM, Mandin RS, Silverman M. Renal Secretion of Vinblastine, Vincristine and Colchicine in vivo. J Pharmacol Exp Ther 1994; 268: 388-395.

    PubMed  Google Scholar 

  169. Okamura N, Hirai M, Tanigawara Y, Tanaka K, Yasuhara M, Ueda K, Komano T, Hori R. Digoxin-cyclosporin A interaction: modulation of the multidrug transporter P-glycoprotein in the kidney. J Pharmacol Exp Ther 1993; 266: 1614-1619.

    PubMed  Google Scholar 

  170. Woodland C, Verjee Z, Giesbrecht E, Koren G, Ito S. The digoxin-propafenone interaction - characterization of a mechanism using renal tubular cell monolayers. J Pharmacol Exp Ther 1997; 283: 39-45.

    PubMed  Google Scholar 

  171. Nierenberg DW. Drug inhibition of penicillin tubular secretion: concoidance between in vitro and clinical findings. J Pharmacol Exp Ther 1987; 240: 712-716.

    PubMed  Google Scholar 

  172. Dupuis L, Loren G, Shore A, Silverman ED, Laxer RM. Methotrexate non-steroidal anti-inflammatory drug interaction in children with arthritis. J Rheumat 1990; 17: 1469-1473.

    Google Scholar 

  173. Banditt P, Meyer FP, Walther H. Influence of cimetidine on the pharmacokinetics of other drugs. Pharmazie 1990; 45: 11-16.

    PubMed  Google Scholar 

  174. Somogyi A, McLean A, Heinzow B. Cimetidine-procainamide pharmacokinetic interac tion in man: evidence of competition for tubular secretion of basic drugs. Eur J Clin Pharmacol 1983; 25: 339-345.

    PubMed  Google Scholar 

  175. Christian CJ, Meredith CG, Speeg KJ. Cimetidine inhibits renal procainamide clearance. Clin Pharmacol Ther 1984; 36: 221-227.

    PubMed  Google Scholar 

  176. Van Crugten J, Bochner F, Keal J, Somogyi A. Selectivety of the cimetidine-induced alterations in the renal handling of organic substrates in humans. Studies with anionic, cationic and zwitterionic drugs. J Pharmacol Exp Ther 1986; 236: 481-487.

    PubMed  Google Scholar 

  177. Gisclon LG, Boyd RA, Williams RL, Giacomini KM. The effect of probenecid on the renal elimination of cimetidine. Clin Pharmacol Exp Ther 1989; 45: 444-452.

    Google Scholar 

  178. Inotsume N, Nishimua M, Nakano M, Fujiyama S, Sato T. The inhibitory effect of probenecid on renal excretion of famotidine in young, healthy volunteers. J Clin Pharmacol 1990; 30: 50-56.

    PubMed  Google Scholar 

  179. Hsyu PH, Gisclon LG, Hui AC, Giacomini KM. Interactions of organic anions with the organic cation transporter in renal BBMV. Am J Physiol 1988; 254: F56-F61.

    PubMed  Google Scholar 

  180. Ott RJ, Hui C, Giacomine KM. Mechanisms of interactions between organic anions and the organic cation transporter in renalbrush border membrane vesicles. Biochem Pharmacol 1990; 40: 659-661.

    PubMed  Google Scholar 

  181. McKinney TD, Myers P, Speeg JKV. Cimetidine secretion by rabbit renal tubules in vitro. Am J Physiol 1981; 241: F69-F76.

    PubMed  Google Scholar 

  182. Brandle E, Greven J. Transport of cimetidine across the basolateral membrane of rabbit kidney proximal tubules: interaction with organic anions. Pharmacology 1992; 45: 231-240.

    PubMed  Google Scholar 

  183. Schück O. Tubular secretion of creatinine and its plasma concentration. Int J Clin Pharmacol Ther Toxicol 1990; 28: 127-128.

    PubMed  Google Scholar 

  184. Sokol PP. Effect of DQ-2556, a new cephalosporin, on organic ion transport in renal plasma membrane vesicles from the dog, rabbit and rat. J Pharmacol Exp Ther 1990; 255: 436-441.

    PubMed  Google Scholar 

  185. Ullrich KJ, Rumrich G, David C, Fritzsch G. Bisubstrates-substances that interact with renal contraluminal organic anion and organic cation transport systems. A. amines, piperidines, piperazines, azepines, pyridines, quinolines, imidazoles, thiazoles, guanidines and hydrazines. Pflügers Arch 1993; 425: 280-299.

    PubMed  Google Scholar 

  186. Chatton JY, Odone M, Besseghir K, Roch-Ramel F. Renal secretion of 3’-azido-3’-deoxythymidine by the rat. J Pharmacol Exp Ther 1990; 255: 140-145.

    PubMed  Google Scholar 

  187. Griffiths DA, Hall SD, Sokol PP. Interaction of 3’-azido-3’-deoxythymidine with organic ion transport in rat renal basolateral membrane vesicles. J Pharmacol Exp Ther 1991; 257: 149-155.

    PubMed  Google Scholar 

  188. Griffiths DA, Hall SD, Sokol PP. Effect of 3’-azido-3’-deoxythymidine (AZT ) on organic ion transport in rat renal brush border membrane vesicles. J Pharmacol Exp Ther 1992; 260: 128-133.

    PubMed  Google Scholar 

  189. Anders MW. Metabolism of drugs by the kidney. Kidney Int 1980; 18: 636-647.

    PubMed  Google Scholar 

  190. Bekersky I, Popick A. Metabolism of bumetanide by the isolated perfused rat kidney. Drug Metab Dispos 1983; 11: 512-513.

    PubMed  Google Scholar 

  191. Bekersky I, Colburn WA. Acetylation of sulfisoxazole by the isolated perfused rat kidney. J Pharm Sci 1980; 69: 1359.

    PubMed  Google Scholar 

  192. Bekersky I, Colburn WA, Fishman L, Kaplan SA. Metabolism of salicylic acid in the isolated perfused rat kidney: interconversion of salicyluric and salicylic acids. Drug Metab Dispos 1980; 8: 319-324.

    PubMed  Google Scholar 

  193. DeLannoy IAM, Nespeca R, Pang KS. Renal handling of enalapril and enala prilat: studies in the isolated red blood cell-perfused rat kidney. J Pharmacol Exp Ther 1989; 251: 1211-1222.

    Google Scholar 

  194. Elseviers MM, De Broe ME. Epidemiology of analgesic nephropathy. J Nephrol 1992; 5: 94-98.

    Google Scholar 

  195. McMurtry RJ, Snodgrass WR, Mitchell JR. Renal necrosis glutathione depletion and covalent binding after acetaminophen. J Toxicol Appl Pharmacol 1978; 46: 87-100.

    Google Scholar 

  196. Mudge GH, Gemborys MW, Duggin GG. Covalent binding of metabolites of acetaminophen to kidney protein and depletion of renal glutathione. J Pharmacol Exp Ther 1978: 206: 218-226.

    PubMed  Google Scholar 

  197. Kleinman JG, Breitenfield RV, Roth DA. Acute renal failure associated with acetaminophen ingestion: report of a case and review of the literature. Clin Nephrol 1980; 14: 201-205.

    PubMed  Google Scholar 

  198. Szefler SJ, Acara M. Isoproterenol excretion and metabolism in the isolated perfused rat kidney. J Pharmacol Exp Ther 1979; 210: 295-300.

    PubMed  Google Scholar 

  199. Rennick B, Ziemniak J, Smith I, Taylor M, Acara M. Tubular transport and metabolism of cimetidine in chicken kidneys. J Pharmacol Exp Ther 1984; 228: 387-392.

    PubMed  Google Scholar 

  200. Bessighir K, Pearce LB, Rennick B. Renal tubular transport and metabolism of organic cations by the rabbit. Am J Physiol 1981; 241: F308-F314.

    Google Scholar 

  201. Watrous WM, May DG, Fujimoto JM. Mechanism of the renal tubular transport of morphine and morphine ethereal sulfate in the chicken. J Pharmacol Exp Ther 1970; 172: 224-229.

    PubMed  Google Scholar 

  202. Hook JB, MacCormack KM, Kluwe WM. Biochemical mechanisms of nephrotoxicity. In: Reviews in biochemi cal toxicology, vol 1. Hodgson, Bend, Philpot (editors). Elsevier/North-Holland, New York 1979; p. 53-78.

    Google Scholar 

  203. Jacqz E, Ward S, Johnson R, Schenker S, Gerkens J, Branch RA. Extrahepatic glucuro nidation of morphine in the dog. Drug Metab Dispos 1986; 14: 627-630.

    PubMed  Google Scholar 

  204. Meffin PJ, Zilm DM, Veendendaal JR. Reduced clofibric acid clearance in renal dysfunction is due to a futile cycle. J Pharmacol Exp Ther 1983; 227: 732-738.

    PubMed  Google Scholar 

  205. Gugler R, Kurten JW, Jensen CJ, Klehr U, Hartlapp J. Clofigrate disposition in renal failure and acute and chronic liver disease. Eur J Clin Pharmacol 1979; 15: 341-347.

    PubMed  Google Scholar 

  206. Verbeeck R, Tjandramaga TB, Mullie A, Verbesselt R, Verberckmoes R, De Schep per PJ. Biotransformation of diflunisal and renal excretion of its glucoroni des in renal insufficiency. Brit J Clin Pharmacol 1979; 7: 273-282.

    Google Scholar 

  207. Eriksson LO, Wahlin-Boll E, Odar-Cederlof I, Lindholm L, Melander A. Influence of renal failure, rheumatoid arthritis and old age on the pharmacokinetics of diflunisal. Eur J Clin Pharmacol 1989; 36: 165-174.

    Google Scholar 

  208. Aronoff GR, Ozawa T, DeSante KA, Nash JF, Ridolfo AS. Benoxaprofen kinetics in renal impairment. Clin Phamacol Ther 1982; 32: 190-194.

    Google Scholar 

  209. Advenier C, Roux A, Gobert C, Massias P, Varaquaux O, Flouvat B. Pharma coki netics of ketoprofen in the elderly. Brit J Clin Pharmacol 1983; 16: 65-70.

    Google Scholar 

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De Broe, M.E., Roch-Ramel, F. (2008). Renal handling of drugs and xenobiotics. In: De Broe, M.E., Porter, G.A., Bennett, W.M., Deray, G. (eds) Clinical Nephrotoxins. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-84843-3_3

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