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Pharmacokinetic Study of Matrine in SD-rat after Oral Administration of KIOM-MA128

SD-rat에 KIOM-MA128을 경구 투여 한 후 혈장 중 Matrine의 약물 동태

  • Received : 2015.02.24
  • Accepted : 2015.05.28
  • Published : 2015.06.30

Abstract

KIOM-MA128 is a novel Korean herbal medicine with anti-atopic, anti-inflammatory and anti-asthmatic effects. This article presents the first pharmacokinetic study on KIOM-MA128. The purpose of this study was to characterize a pharmacokinetic characteristic of matrine, a potential marker of KIOM-MA128, in rats using population pharmacokinetic model. 1, 2 and 8 g/kg of KIOM-MA128 were administered to rats orally and plasma concentrations of matrine was determined by HPLC-MS/MS. Non-compartmental analysis (NCA) was performed using Phoenix$^{(R)}$ and pharmacokinetic model was built using NONMEM$^{(R)}$. This model was validated with internal validation which is visual predictive check (VPC) and bootstrap. The NCA result of matrine showed that $C_{max}$ was 294.24, 552.22 and 868.65 ng/ml, $AUC_{inf}$ was 1273.05, 2724.76 and $9743.25ng{\cdot}hr/ml$ and $T_{max}$ was 1, 1.3 and 2.3 hr for the doses of 1, 2, and 8 g/kg, respectively. The rat plasma concentrations were described very well with one-compartment model. Pharmacokinetic model for matrine was successfully developed and evaluated. Finally, our model is helpful to understand pharmacokinetic characteristic of KIOM-MA128.

Keywords

References

  1. 조민서, 한재경, 김윤희 : 한방병원 소아과를 내원한 소아 아토피 피부염 환자 실태에 관한 조사. 대한한방소아과학회지 25, 8 (2011).
  2. DaVeiga, S. P. : Epidemiology of atopic dermatitis: A review. Allergy Asthma Proc. 33, 227 (2012). https://doi.org/10.2500/aap.2012.33.3569
  3. 2011 국민건강통계 국민건강영양조사 제 5기 2차년도. 보건복지부 질병관리본부 (2011).
  4. 오재원, 김규언, 편복양, 이혜란, 정지태, 홍수종, 박강서, 이수영, 송상욱, 김철봉, 안강모, 남승연, 손명현, 김우경, 이미희, 차병철, 최성연, 이소연, 이하백, 이상일, 이준성 : 1995년과 2000년의 학동기와 2003년 학동전기 소아에서의 아토피피부염의 역학적 변화에 관한 전국적인 연구. 소아알레르기 및 호흡기 학회지 13, 227 (2003).
  5. Oak, J. W. and Lee, H. S, : Prevalence rate and factors associated with atopic dermititis among korean middle school students. J Korean Acad Nurs. 42, 992 (2012). https://doi.org/10.4040/jkan.2012.42.7.992
  6. Chung, T. H., Kang, T. J., Cho, W. K., Im, G. Y., Lee, G. S., Yang, M. C., Cho, C. W. and Ma, J. Y. : Effectiveness of the novel herbal medicine, KIOM-MA, and its bioconversion product, KIOM-MA128, on the treatment of atopic dermatitis. Evid Based Complement Alternat Med. 2012 (2012).
  7. Liu, J. Y., Hu, J. H., Zhu, Q. G., Li, F. Q., Wang, J. and Sun, H. J. : Effect of matrine on the expression of substance P receptor and inflammatory cytokines production in human skin keratinocytes and fibroblasts. Int Immunopharmacol. 7, 816 (2007). https://doi.org/10.1016/j.intimp.2007.02.003
  8. Stander, S. and Luger, T. A. : Itch in atopic dermatitis - pathophysiology and treatment. Acta Dermatovenerol Croat. 18, 289 (2010).
  9. Kim, D.-S., Kim, S.-H., Kim, B.-K., Yang, M. C. and Ma, J. Y. : Antiasthmatic effects of herbal complex MA and its fermented product MA128. Evid Based Complement Alternat Med. 2012 (2012).
  10. Guidance for Industry Botanical Drug Products. Food and Drug Administration (2004).
  11. Back, H.-m., Song, B., Chae, J.-w., Yun, H.-y., Ma, J. Y. and Kwon, K.-i. : Determination of matrine in rat plasma after oral administration of novel korean herbal medicine KIOM-MA128 and application of PK. J Anal Methods Chem. 2015 (2015).
  12. Parke, J., Holford, N. H. and Charles, B.G. : A procedure for generating bootstrap samples for the validation of nonlinear mixed effects population models. Compu.t Methods Programs Biomed. 59, 19 (1999). https://doi.org/10.1016/S0169-2607(98)00098-4
  13. Iwi, G., Millard, R. K., Palmer, A. M., Preece, A. W. and Saunders, M. : Bootstrap resampling: a powerful method of assesing confidence intervals for doses from experiment data. Phys. Med. Biol. 44, 55 (1999). https://doi.org/10.1088/0031-9155/44/4/021
  14. Lawrence, X. Y. and Gordon, L. A. : Saturable small intestinal drug absorption in humans: modeling and interpretation of cefatrizine data. Eur. J. Pharm. Biopharm. 45, 199 (1998). https://doi.org/10.1016/S0939-6411(97)00088-X
  15. Yang, Z., Gao, S., Yin, T., Kulkarni, K. H., Teng, Y., You, M. and Hu, M. : Biopharmaceutical and pharmacokinetic characterization of matrine as determined by a sensitive and robust UPLC-MS/MS method. J. Pharm. Biomed. Anal. 51, 1120 (2010). https://doi.org/10.1016/j.jpba.2009.11.020
  16. Zhang, L., Liu, W., Zhang, R., Wang, Z., Shen, Z., Chen, X. and Bi, K. : Pharmacokinetic study of matrine, oxymatrine and oxysophocarpine in rat plasma after oral administration of Sophora flavescens Ait. extract by liquid chromatography tandem mass spectrometry. J. Pharm. Biomed. Anal. 47, 892 (2008). https://doi.org/10.1016/j.jpba.2008.03.019
  17. Sun, Y. G., Du, Y. F., Yang, K., Chang, L., Cao, L., Ren, Y. P., Sun, Q., Wang, Q., Zhang, L. T. and Lv, P. T. : A comparative study on the pharmacokinetics of a traditional Chinese herbal preparation with the single herb extracts in rats by LC-MS/MS method. J. Pharm. Biomed. Anal. 81-82, 34 (2013). https://doi.org/10.1016/j.jpba.2013.03.022
  18. 한약(생약)제제 비임상시험 가이드라인(Guideline on the Nonclinical Studies of Herbal Drug Products). 식품의약품안전처 (2014).
  19. Diehl, K. H., Hull, R., Morton, D., Pfister, R., Rabemampianina, Y., Smith, D., Vidal, J. M. and van de Vorstenbosh, C. : A good practice guide to the administration of substances and removal of blood, including routes and volumes. J. Appl. Toxicol. 21, 15 (2001). https://doi.org/10.1002/jat.727