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Pharmacokinetics and the Intestinal Permeability of Amaranth in Rats

적색식용색소인 아마란스의 약동학 특성 및 위장관 투과도 연구

  • Han, Youjin (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University) ;
  • Goo, Soo Hyeon (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University) ;
  • Nam, So Jeong (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University) ;
  • Kang, Yun Ju (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University) ;
  • Kwon, Mihwa (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University) ;
  • Song, Im-Sook (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University)
  • Received : 2017.02.16
  • Accepted : 2017.07.16
  • Published : 2017.07.30

Abstract

Although amaranth, a red-colored tar dye, is usually used in foods, cosmetics, and pharmaceutics, its bioavailability and intestinal absorption have not previously been investigated. Therefore, the purpose of this study was to investigate the pharmacokinetics properties and intestinal permeability of amaranth in rats following the intravenous and oral administration of this dye. Amaranth rapidly disappeared from the plasma following the intravenous injection, with a half-life of 38.8 minutes. However, the plasma concentration of amaranth was increased to 400 minutes following the oral administration of amaranth, and the absorption time and bioavailability of amaranth were calculated to be 356 minutes and 55.6%, respectively. This suggests that once amaranth exists in the gut, this dye may be efficiently and effectively absorbed. Consistent with this result, the intestinal permeability of amaranth was comparable to atenolol, a marker compound of moderate permeability, and to one-third of caffeine's intestinal permeability (a highly permeable compound). In conclusion, a significantly long absorption time and substantial intestinal absorption of amaranth was observed following the oral administration of amaranth at a dose of 300 mg/kg in rats, despite the rapid elimination of this dye from the plasma. These results may suggest the necessity of a careful and limited use of amaranth dye when it is added to food, lip-care cosmetics, and orally administered pharmaceutics.

적색 아조류 타르색소인 아마란스는 인공식용색소로 식품, 화장품, 의약품에 광범위하게 사용되고 있음에도 불구하고, 경구로 복용하였을 때 위장관 흡수율이나 흡수특성에 대해 연구된 바가 없다. 본 연구의 목적은 아마란스의 정맥투여 또는 경구 투여 후 약동학 특성을 평가하고 diffusion chamber system을 이용하여 위장관 흡수율 및 투과도를 평가하고자 하였다. 정맥투여된 아마란스는 38.8분의 소실반감기로 빠르게 혈중에서 소실된다. 그러나 경구투여된 아마란스는 생체이용률도 55.6%로 높은 위장관 흡수율을 나타내며 408분까지 혈중농도가 증가하고 24시간까지 혈중에 남아있는 특성을 나타내었다. 이는 아마란스의 위장관 흡수가 오랫동안 지속적으로 일어나는 것을 의미한다. 이를 확인하기 위하여 소장의 흡수부위를 공장, 회장사부, 회장하부로 나누어 위장관 투과도를 평가하고 투과성이 잘 알려진 지표물질과 비교하였다. 연구결과 아마란스의 위장관투과성은 투과도가 매우 높은 caffeine의 1/3정도의 투과도를 보이고, 중등도의 투과도를 보이는 atenolol과 유사한 투과도를 나타내었으며 회장상부에서의 투과도가 가장 높았다. 결과를 종합하면, 아마란스는 경구투여된 뒤 지속적으로 흡수되며 흡수율도 50% 이상을 보이므로, 식품, 립케어 화장용품, 경구용 의약품에 아마란스 등의 색소가 포함될 경우에는 첨가량 등을 고려하여 신중하게 사용해야 할 것이다.

Keywords

References

  1. Choi, Y. A., Yoon, Y. H., Choi, K., Kwon, M., Goo, S. H., Cha, J. S., Choi, M. K., Lee, H. S. and Song, I. S. 2015. Enhanced oral bioavailability of morin administered in mixed micelle formulation with pluronicf127 and tween80 in rats. Biol. Pharm. Bull. 38, 208-217. https://doi.org/10.1248/bpb.b14-00508
  2. Jung, D., Mroszczak, E. and Bynum, L. 1988. Pharmacokinetics of ketorolac tromethamine in humans after intravenous, intramuscular and oral administration. Eur. J. Clin. Pharmacol. 35, 423-425. https://doi.org/10.1007/BF00561376
  3. Kim, K. J., Kim, J. Y., Park, S., Bang, J. S. and Lee, W. 2013. Investigation for the management methods of pure tar color additives for drugs and quasi-drugs. Kor. J. Clin. Pharm. 23, 97-105.
  4. Levin, V. A. 1980. Relationship of octanol/water partition coefficient and molecular weight to rat brain capillary permeability. J. Med. Chem. 23, 682-684. https://doi.org/10.1021/jm00180a022
  5. Paghdal, K. V. and Schwartz, R. A. 2009. Topical tar: Back to the future. J. Am. Acad. Dermatol. 61, 294-302. https://doi.org/10.1016/j.jaad.2008.11.024
  6. Park, H. W., Park, C. H., Park, S. H., Park, J. Y., Park, H. S., Yang, H. J., Ahn, K. M., Kim, K. H., Oh, J. W., Kim, K. E., Pyun, B. Y., Lee, H. B. and Min, K. U. 2008. Dermatologic adverse reactions to 7 common food additives in patients with allergic diseases: A double-blind, placebo- controlled study. J. Allergy Clin. Immunol. 121, 1059-1061. https://doi.org/10.1016/j.jaci.2007.12.1162
  7. Park, S. K., Lee, D. S. and Park, S. K. 2005. Estimation of daily dietary intake of food red colors - food red no.2, no.3 and no. 40. J. Kor. Soc. Food Sci. Nutr. 34, 75-80. https://doi.org/10.3746/jkfn.2005.34.1.075
  8. Phillips, J. C., Bex, C. S., Mendis, D., Walters, D. G. and Gaunt, I. F. 1987. Metabolic disposition of 14c-labelled amaranth in the rat, mouse and guinea-pig. Food Chem. Toxicol. 25, 947-954. https://doi.org/10.1016/0278-6915(87)90288-2
  9. Ruddick, J. A., Craig, J., Stavric, B., Willes, R. F. and Collins, B. 1979. Uptake distribution and metabolism of [14c]amaranth in the female rat. Food Cosmet. Toxicol. 17, 435-442. https://doi.org/10.1016/0015-6264(79)90001-4
  10. Shimada, C., Kano, K., Sasaki, Y. F., Sato, I. and Tsudua, S. 2010. Differential colon DNA damage induced by azo food additives between rats and mice. J. Toxicol. Sci. 35, 547-554. https://doi.org/10.2131/jts.35.547
  11. Simon, R. A. 2003. Adverse reactions to food additives. Curr. Allergy Asthma. Rep. 3, 62-66. https://doi.org/10.1007/s11882-003-0014-9
  12. Song, I. S., Choi, Y. A. and Choi, M. K. 2017. Comparison of gastrointestinal permeability of caffeine, propranolol, atenolol, ofloxacin, and quinidine measured using ussing chamber system and caco-2 cell monolayer. Mass Spectrom Lett. 8, 34-38.
  13. Stewart, B. H., Chan, O. H., Lu, R. H., Reyner, E. L., Schmid, H. L., Hamilton, H. W., Steinbaugh, B. A. and Taylor, M. D. 1995. Comparison of intestinal permeabilities determined in multiple in vitro and in situ models: Relationship to absorption in humans. Pharm. Res. 12, 693-699. https://doi.org/10.1023/A:1016207525186
  14. Takahashi, K., Wada, T., Higashi, Y. and Yata, N. 1985. Pharmacokinetics in hepatic transport of amaranth in rats intoxicated with carbon tetrachloride and alpha-naphthylisothiocyanate. Chem. Pharm. Bull (Tokyo) 33, 4973-4980. https://doi.org/10.1248/cpb.33.4973
  15. Tsuda, S., Murakami, M., Matsusaka, N., Kano, K., Taniguchi, K. and Sasaki, Y. F. 2001. DNA damage induced by red food dyes orally administered to pregnant and male mice. Toxicol. Sci. 61, 92-99. https://doi.org/10.1093/toxsci/61.1.92
  16. Watabe, T., Ozawa, N., Kobayashi, F. and Kurata, H. 1980. Reduction of sulphonated water-soluble azo dyes by micro-organisms from human faeces. Food Cosmet. Toxicol. 18, 349-352. https://doi.org/10.1016/0015-6264(80)90187-X