Dose dependency in the oral bioavailability of an organic cation model, tributylmethyl ammonium (TBuMA), in rats: Association with the saturation of efflux by the P-gp system on the apical membrane of the intestinal epithelium

Journal of Pharmaceutical Sciences

Volumn 94, Issue 12, 2005, Pages 2644-2655

  Kim, Moon Kyoung ^a   Han, Liwei ^b   Choi, Min Koo ^a   Han, Yong Hae ^c   Kim, Dae Duk ^a   Chung, Suk Jae ^a   Shim, Chang Koo ^a  

^a Seoul National University   (South Korea)

^b BEIJING UNIVERSITY OF CHINESE MEDICINE   (China)

^c BRISTOL MYERS SQUIBB   (United States)

Author keywords

Efflux pumps; Intestinal secretion transport; Nonlinear pharmacokinetics; Organic cation transporters (OCT); Organic cations (OCs); P glycoprotein (P gp); TBuMA; Ussing chamber

Indexed keywords

CATION; DIGOXIN; GLYCOPROTEIN P; MANNITOL; ORGANIC CATION TRANSPORTER; ORGANIC CATION TRANSPORTER 1; ORGANIC CATION TRANSPORTER 3; RHODAMINE 123; TRIBUTYLMETHYLAMMONIUM; VERAPAMIL;

ANIMAL EXPERIMENT; ANIMAL TISSUE; APICAL MEMBRANE; ARTICLE; ARTIFICIAL MEMBRANE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG TRANSPORT; EPITHELIUM CELL; ILEUM; INTESTINE EPITHELIUM; INTESTINE SECRETION; JEJUNUM; MALE; MODEL; NONHUMAN; NONLINEAR SYSTEM; PLASMA PROTEIN BINDING; RAT; TEMPERATURE DEPENDENCE;

EID: 33144459022     PISSN: 00223549     EISSN: 15206017     Source Type: Journal    
DOI: 10.1002/jps.20456     Document Type: Article

References (46)

1. Neuhoff S, Ungell AL, Zamora I, Artursson P. 2003. pH-dependent bidirectional transport of weakly basic drugs across Caco-2 monolayers: implications for drug-drug interactions. Pharm Res 20:1141-1148.
2. Okuda M, Saito H, Urakami Y, Takano M, Inui KI. 1996. cDNA cloning and functional expression of a novel organic cation transporter, OCT2. Biochem Biophys Res Commun 224:500-507.
3. Gorboulev V, Ulzheimer JC, Akhoundova A, Ulzheimer-Teuber I, Karbach U, Quester S, Baumann C, Lang F, Busch AE, Koepsell H. 1997. Cloning and characterization of two human polyspecific organic cation transporters. DNA Cell Biol 16:871-881.
4. Zhang L, Dresser MJ, Gray AT, Yost SC, Terashita S, Giacomini KM. 1997. Cloning and functional expression of a human liver organic cation transporter. Mol Pharmacol 51:913-921.
5. Kekuda R, Prasad PD, Wu X, Wang H, Fei YJ, Leibach FH, Ganapathy V. 1998. Cloning and functional characterization of a potential-sensitive, polyspecific organic cation transporter (OCT3) most abundantly expressed in placenta. J Biol Chem 273:15971-15979.
6. Grundemann D, Schechinger B, Rappold GA, Schomig E. 1998. Molecular identification of the corticosterone-sensitive extraneuronal catecholamine transporter. Nat Neurosci 1:349-351.
7. Yabuuchi H, Tamai I, Nezu JI, Sakamoto K, Oku A, Shimane M, Sai Y, Tsuji A. 1999. Novel membrane transporter OCTN1 mediated multi-specific, bidirectional, and pH-dependent transport of organic cations. J Pharmacol Exp Ther 289:768-773.
8. Wu X, Huang W, Prasad PD, Seth P, Rajan DP, Leibach FH, Chen J, Conway SJ, Ganapathy V. 1999. Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), and organic cation/carnitine transporter. J Pharmacol Exp Ther 290:1482-1492.
9. Zhang L, Schaner ME, Giacomini KM. 1998. Functional characterization of an organic cation transporter (hOCT1) in a transiently transfected human cell line (HeLa). J Pharmacol Exp Ther 286: 354-361.
10. Tamai I, Ohashi R, Nezu J, Sai Y, Kobayashi D, Oku A, Shimane M, Tsuji A. 2000. Molecular and functional characterization of organic cation/carnitine transporter family in mice. J Biol Chem 275: 40064-40072.
11. Dresser MJ, Gray AT, Giacomini KM. 2000. Kinetic and selectivity differences between rodent, rabbit, and human organic cation transporters (OCT1). J Pharmacol Exp Ther 292:1146-1152.
12. Okuda M, Urakami Y, Saito H, Inui KI. 1999. Molecular mechanisms of organic cation transport in OCT2-expressing Xenopus oocytes. Biochim Biophys Acta 1417:224-231.
13. Israili ZH, Dayton PG. 1984. Enhancement of xenobiotic elimination: role of intestinal excretion. Drug Metab Rev 15:1123-11359.
14. Koepsell H, Schmitt BM, Gorboulev V. 2003. Organic cation transporter. Rev Physiol Biochem Pharmacol 150:36-90.
15. Moon SC. 2001. MS Thesis, The absorption mechanism of tributylmethyl ammonium. A model quaternary ammonium in the small intestine. Seoul National University, Seoul, Korea. http://147.46.181.136/snudl2/000000070000/SVC/ 000000065078/000000065078000000000001.pdf
16. Smit JW, Weert B, Schinkel AH, Meijer DKF. 1998. Heterologous expression of various P-glycoproteins in polarized epithelial cells induces directional transport of small (type 1) and bulky (type 2) cationic drugs. J Pharmacol Exp Ther 286:321-327.
17. Li LY, Amidon GL, Kim JS, Heimbach T, Kesisoglou F, Topliss JT, Fleisher D. 2002. Intestinal metabolism promotes regional differences in apical uptake of indinavir: coupled effect of P-glycoprotein and cytochorme P450 3A on indinavir membrane permeability in rat. J Pharmacol Exp Ther 301: 586-593.
18. Grundemann D, Gorboulev V, Gamberyan S, Veyhl M, Koepsell H. 1994. Drug excretion mediated by a new prototype of polyspeciflc transporter. Nature 372:549-552.
19. 2 receptor antagonists cimetidine and ranitidine by P-glycoprotein in rat intestine and the human colonic cell line Caco-2. J Pharmacol Exp Ther 288:171-178.
20. Zhu C, Jiang L, Chen TM, Hwang KK. 2002. A comparative study of artificial membrane permeability assay for high throughput profiling of drug absorption potential. Eur J Med Chem 37:399-407.
21. Gibaldi M, Perrier D. 1982. Pharmacokinetcis, 2nd ed. New York: Marcel Dekker, Inc., pp 1-111.
22. Yu IL, Chung SJ, Lee MH, Shim CK. 1997. Pharmacokinetics of 1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-1-piperazinyl)-1, 4-dihydro-4-oxoquinolone-3-carboxylic acid hydrocholoride (DW-116), a new quinolone antibiotics in rats. J Pharm Sci 86:550-553.
23. Song IS, Chung SJ, Shim CK. 1999. Different activity of ATP dependent transport across the canalicular membrane for tributylmethylammonium and triethylmethyl ammonium as a potential mechanism of the preferential biliary excretion for tributylmethylammonium in the rat. Pharm Res 16:540-544.
24. Nagahara M, Tavelin S, Artursson P. 2004. Contribution of the paracellular route to the pH-dependent epithelial permeability to cationic drugs. J Pharm Sci 93:2972-2984.
25. Dressman JB, Amidon GL, Reppas C, Shah VP. 1998. Dissolution testing as a prognostic tool for oral drug absorption: immediate release dosage forms. Pharm Res 15:11-22.
26. Kuo SM, Whitby BR, Artursson P, Ziemniak JA. 1994. The contribution of intestinal secretion the the dose-dependent absorption of celiprolol. Pharm Res 11:648-653.
27. Harrison A, Betts A, Fenner K, Beaumont K, Edgington A, Roffey S, Davis J, Comby P, Morgan P. 2004. Nonlinear oral pharmacokinetics of the a-antagonist 4-amoni-5-(4-fluorophenyl)-6,7-dimethoxy-2-[4-(morpholinocarbonly)-perhydro-1, 4-diazepin-1-yl]quinolone in humans: use of preclinical data to rationalize clinical observation. Drug Metab Dispos 32:197-204.
28. Hsing S, Gatmaitan Z, Arias IM. 1992. The function of Gp170, the multidrug-resistance gene product, in the brush border of rat intestinal mucosa. Gastroenterology 102:879-885.
29. Saito H, Aungst BJ. 1995. Possible involvement of multiple P-glycoprotein mediate efflux systems in the transport of verapamil and other organic cations across rat intestine. Pharm Res 12:1304-1310.
30. Thiebaut F, Tsuruo T, Hamada H, Gottesman MM, Pastan L, Willingham MC. 1987. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal tissues. Proc Natl Acad Sci 84:7735-7738.
31. Meserruw R, Moons MM, Russel F. 1997. Rhodamine 123 accumulates extensively in the isolated perfused rat kidney and is secreted by the organic cation system. Eur J Pharmacol 321:315-323.
32. Smit JW, Schinkel AH, Muller M, Weert B, Meijer DKF. 1998. Contribution of the murine mdr1a P-glycoprotein to hepatobiliary and intestinal elimination of cationic drugs as measured in mice with an mdr1a gene distruption. Hepatology 27:1056-1063
33. Montfoort JEV, Muller M, Groothuis GMM, Meijer DKK, Koepsell H, Meier PJ. 2001. Comparison of "type I" and "type II" organic cation transport by organic cation transporters and organic anion transporting polypeptides. J Pharmacol Exp Ther 298:110-115.
34. Koepsell H. 2004. Polyspecific organic cation transporters: their functions and interactions with drugs. Trends Pharmacol Sci 25:375-381.
35. Ohashi R, Tamai I, Nezu JI, Nikaido H, Hashimoto N, Oku A, Sai Y, Shimane M, Tsuji A. 2001. Molecular and physiological evidence for multifunctionality of canitine/organic cation transporter OCTN2. Mol Pharmacol 59:358-366.
36. Katsura T, Inui KI. 2003. Intestinal absorption of drugs mediated by drug transporters: mechanisms and regulation. Drug Metab Pharmacokin 18:1-15.
37. Wu X, George RL, Huang W, Wang H, Conway SJ, Leibach FH, Ganapathy V. 2000. Structual and functional characteristics and tissue distribution pattern of rat OCTN1, and organic cation transporter, cloned from placenta. Biochim Biophy Acta 1466:315-327
38. Wu X, Kekuda R, Huang W, Fei YJ, Leibach FH, Chen J, Conway SJ, Ganapathy V. 1998. Identity of the organic cation transporter OCT3 as the extraneuronal monoamine transporter (uptake2) and evidence for the expression of the transporter in the brain. J Biol Chem 273:32776-32786.
39. Slitt AL, Cherrington NJ, Hartley DP, Leazer TM, Klaassen CD. 2002. Tissue distribution and renal developmental changes in rat organic cation transporter mRNA levels. Drug Metab Dispos 30:212-219.
40. Okuda M, Urakami Y, Saito H, Inui K. 1999. Molecular mechanisms of organic cation transport in OCT2-expressing Xenopus oocytes. Biochi, Biophys Acta 1417:224-231.
41. Urakami Y, Okuda M, Masuda S, Saito H, Inui KI. 1998. Functional characteristics and membrane localization of rat multispecific organic cation transporters, OCT1 and OCT2, mediating tubular secretion of cationic drugs. J Pharmacol Exp Ther 287:800-805.
42. Wu X, George RL, Huang W, Wang H, Conway SJ, Leibach FH, Ganapathy V. 2000. Structual and functional characteristics and tissue distribution pattern of rat OCTN1, and organic cation transporter, cloned from placenta. Biochim Biophy Acta 1466:315-327.
43. Martel F, Vetter T, Russ H, Grundemann D, Azevedo I, Koepsell H, Schomig E. 1996. Transport of small organic cations in the liver. The role of the organic cation transporter OCT1. Naunyn Schmiedeberg's Arch Pharmacol 354:320-326.
44. +-dependent organic cation transport mechanism. Br J Pharmacol 129:615-619.
45. Zhang L, Gorset W, Dresser MJ, Giacomini KM. 1999. The interaction of n-tetraalkylammonium compounds with a human organic cation transporter, hOCT1. J Pharmacol Exp Ther 288:1192-1198.
46. Artursson P, Karlsson J. 1991. Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco cells). Biochem Biophys Res Commun 175:880-885.