摘要
目的探讨新型全反式维甲酸(ATRA)衍生物4-氨基-2-三氟甲基苯基维甲酸酯(ATPR)的在体肠吸收特性。方法建立大鼠在体单向肠灌流模型并采用高效液相色谱(HPLC)法测定灌流液中的ATPR、ATRA的浓度,分别计算100、250、500、1 000 mg/L ATPR在空肠及ATPR、ATRA在不同肠段的吸收速率常数(K a)和有效渗透系数(P eff)。结果随着ATPR浓度的增加,其K a、P eff值分别为(6.77±1.84)×10-3、(14.85±3.46)×10-3、(12.48±3.15)×10-3、(3.03±0.73)×10-3/s和(0.61±0.17)×10-3、(1.41±0.25)×10-3、(1.23±0.30)×10-3、(0.29±0.07)×10-3cm/s,均先增加后减小,存在高浓度饱和现象。灌流液在各肠段(十二指肠、空肠、回肠和结肠)的K a和P eff差异均无显著性(P>0.05),且与ATRA在4个肠段的K a和P eff比较差异无显著性(P>0.05)。结论 ATPR在大鼠肠道内的吸收机制可能为主动转运或易化扩散,且在全肠段内无特定吸收窗。
Objective To investigate the intestinal absorption characterization of a novel derivative of all-trans retinoic acid, 4-amino-2-trifluoromethyl-phenyl retinate （ATPR） in rats. Methods The absorption characterization was evaluated by using in situ single pass intestinal perfusion model and the concentration of ATPR and ATRA in the perfusion samples was determined by HPLC method. The absorption rate constants （Ka） and effective permeability coefficients （Pelf） of 100, 250, 500, 1 000 mg/L of ATPR in jejunum and of ATPR and ATRA in the four segments of the rat intestine were calculated, respectively. Results The Ka and Peff of ATPR which first increased and then decreased （P 〈 0. 05 ） with the increase of drug concentration were （6.77 ±1.84） ×10^-3, （ 14. 85 ±3.46） ×10^-3, （12.48 ±3.15） ×10^-3, （3.03 ±0.73） ×10^-3/sand （0.61±0.17） ×10^-3, （1.41 ±0.25） x 10 -3, （ 1.23 ±0. 30） x 10 -3, （0. 29 ±0. 07）×10^-3 cm/s, respectively, existing the saturate absorption phenomena. The K and Peff had no significant difference （ P 〉 0. 05 ） in the four intestinal segments and compared with those of ATRA. There was no significant difference （P 〉 0. 05 ） in the four intestinal segments. Conclusion The intestinal absorption of ATPR is probably an active transport or facilitated diffusion process with a good absorption in the whole intestinal sections.
出处
《安徽医科大学学报》
CAS
北大核心
2014年第1期67-71,共5页
Acta Universitatis Medicinalis Anhui
基金
"重大新药创制"科技重大专项(编号:2011ZX09401)
安徽省高校优秀青年人才基金资助项目(编号:2011SQRL062)
