盐酸度洛西汀大鼠离体肠吸收动力学

目的考察盐酸度洛西汀在大鼠各肠段的吸收特征。方法采用离体外翻肠囊法，以HPLC法测定不同浓度的盐酸度洛西汀在大鼠各肠段的吸收量，并分别计算吸收速率常数（ka）和表观渗透系数（Papp）；同法考察了P-糖蛋白抑制剂（维拉帕米和环孢素A）对盐酸度洛西汀肠道吸收的影响。结果药物浓度对大鼠各肠段ka没有明显影响；ka按空肠、回肠、十二指肠、结肠依次减小，分别为（2．64±0．17）、（2．15±0．11）、（1．24±0．04）和（0．88±0．09）·h^-1，药物吸收符合一级动力学特征，吸收机制为被动扩散；P。按空肠、回肠、十二指肠和结肠依次减小，分别为（5．59±1．69）×10^-5、（4．88±1．38）×10^-5、（3．08±1．05）和（2．66±0．70）×10^-5cm·8^-1；P-糖蛋白抑制剂对吸收没有明显影响。结论盐酸度洛西汀吸收窗比较长，适合制成肠溶制剂，也提示可以制成在肠道中缓释的制剂。

Study on the rat intestinal absorption kinetics of duloxetine hydrochloride in vitro

MM To study the absorption characteristics of duloxetine hydrochloride （DH） in rats＇ intestines. METHODS Everted intestinal sacs were used to study the absorption characteristics of DH in rats. The concentration of DH was determined by HPLC, then the constant of absorption rate（ ka）and the apparent permeability coeiticient （Papp） were calculated. Same method was applied in investigating the impact of the P-glycoprotein inhibitors （verapamil and cy- closporin A） on the absorption of DH in intestinal segments. RESULTS It was showed that the concentration of DH did not significantly influence the constant of absorption rate of DH, the order of absorption rate was jejunum 〉 ileum 〉 duodenum〉 colon and corresponding values were （2.64 ± 0. 17）, （2.15±0.11）, （1.24± 0.04） and （0.88± 0.09）· h- 1, respectively. The results indicated that the absorption of DH complied with the first order kinetics and the passive transport mechanism. The order of the P~pp was jejunum 〉 ileum 〉 duodenum 〉 colon, corresponding values were （5.59±1.69）·10^-5, （4.88± 1.38）·10^-5, （3.08±1.05）·10^-5 and （2.66±0.70）·10^-5 cm·s^-1,respectively. P-glycoprotein inhibitors （verapamil and cyclosporin A） did not significantly influence the absorption of DH. CONCLU- SION DH is well absorbed in the whole intestine, and it is suitable to be prepared as enteric-coated dosage form. The results indicate that DH can be prepared into sustained-release dosage form in intestines.