结论

胃肠道pH值和缓冲容量的种间差异是重要的考虑因素，尤其是对胃肠道给药的pHresponsive配方和可电离药物。 因此，兔子和猪的空肠、回肠和近端结肠具有相对较高的缓冲容量，而猪远端结肠具有较低的缓冲容量是非常重要的考虑因素。 与人相比，大鼠、兔和猪的近端小肠和升结肠的液体的渗透压和表面张力也较高。 胃肠道特征的这些差异导致泼尼松龙在大鼠体内的溶解度较高（近端结肠除外），而泼尼松龙在猪和兔体内的溶解度与人类相当。 因此，如果在大鼠的体液中测量，中性化合物泼尼松龙的溶解度可能被高估。 另一方面，可电离药物美沙拉秦在兔和猪体内的溶解度在小肠中部高于人，在结肠中低于人，仅在小肠远端与人相当。 胃肠道环境的差异，如pH值、缓冲容量、渗透压和表面张力，导致药物溶解度的差异。 在兔子和猪中，美沙拉秦的溶解度在沿胃肠道向下移动时发生显著变化，这在很大程度上受管腔液的pH值和渗透压的影响。

工具书类

1. Flaisher-Grinberg S et al. Models of mania: from facets to domains and from animal models to model animals. J Psychopharmacol 2010; 24: 437–438.

2. Insel TR. From animal models to model animals. Biol Psychiatry 2007; 62: 1337–1339.

3. Hannah-Poquette C et al. Modeling mania: further validation for Black Swiss mice as model animals. Behav Brain Res 2011; 223: 222–226.

4. Calabrese EJ. Gastrointestinal and dermal absorption – interspecies differences. Drug Metab Rev 1984; 15: 1013–1032.

5. Kararli TT. Comparison of the gastrointestinal anatomy, physiology, and biochemistry of humans and commonly used laboratory-animals. Biopharm Drug Dispos 1995; 16: 351–380.

6. McConnell EL et al. Measurements of rat and mouse gastrointestinal pH, fluid and lymphoid tissue, and implications for in-vivo experiments. J Pharm Pharmacol 2008; 60: 63–70.

7. Ward FW, Coates ME. Gastrointestinal pH measurement in rats: influence of the microbial flora, diet and fasting. Lab Anim 1987; 21: 216–222.

8. Smith HW. Observations on the Flora of the alimentary tract of animals and factors affecting its composition. J Pathol Bacteriol 1965; 89: 95–122.

9. Clarysse S et al. Postprandial evolution in composition and characteristics of human duodenal fluids in different nutritional states. J Pharm Sci 2009; 98: 1177–1192.

10. Kalantzi L et al. Characterization of the human upper gastrointestinal contents under conditions simulating bioavailability/bioequivalence studies. Pharm Res 2006; 23: 165–176.

11. Fadda HM et al. Drug solubility in luminal fluids from different regions of the small and large intestine of humans. Mol Pharm 2010; 7: 1527– 1532.

12. Merchant HA et al. Assessment of gastrointestinal pH, fluid and lymphoid tissue in the guinea pig, rabbit and pig, and implications for their use in drug development. Eur J Pharm Sci 2011; 42: 3–10.

13. ToxNet. Mesalamine: Toxicology data network (ToxNet). US National Library of Medicine, CASRN: 89-57-6. 2014. (http://toxnet.nlm.nih.gov/cgi-bin/sis/ search2/r?dbs+hsdb:@term+@rn+@ rel+89-57-6, last accessed 25th June 2014).

14. Machatha SG, Yalkowsky SH. Comparison of the octanol/water partition coefficients calculated by ClogP, ACDlogP and KowWin to experimentally determined values. Int J Pharm 2005; 294: 185–192.

15. McConnell EL et al. Gut instincts: explorations in intestinal physiology and drug delivery. Int J Pharm 2008; 364: 213–226.

16. Mudie DM et al. Physiological parameters for oral delivery and in vitro testing. Mol Pharm 2010; 7: 1388– 1405.

17. French DL, Mauger JW. evalsuation of the physicochemical properties and dissolution characteristics of mesalamine: relevance to controlled intestinal drug delivery. Pharm Res 1993; 10: 1285–1290.

18. Perez de la Cruz Moreno M et al. Characterization of fasted-state human intestinal fluids collected from duodenum and jejunum. J Pharm Pharmacol 2006; 58: 1079–1089. 19. Diakidou A et al. Characterization of the contents of ascending colon to which drugs are exposed after oral administration to healthy adults. Pharm Res 2009; 26: 2141–2151.

Delta-8 动物胃肠道体内中药物的溶解度的测定——摘要、介绍

Delta-8 动物胃肠道体内中药物的溶解度的测定——材料和方法

Delta-8 动物胃肠道体内中药物的溶解度的测定——结果和讨论

Delta-8 动物胃肠道体内中药物的溶解度的测定——结论、致谢！