盐酸帕罗西汀大鼠在体肠吸收动力学研究

 目的研究盐酸帕罗西汀(paroxetine hydrochloride,PRXT)在大鼠消化道各部位的吸收动力学。方法运用在体循环灌流模型,研究大鼠消化道各部位对PRXT的吸收情况,计算和比较K_a值,并分析剂量和流速对结果的影响。结果PRXT在大鼠十二指肠、空肠、回肠、结肠吸收速率常数Ka基本一致(P>0.05),不同剂量条件下各部位吸收速率无显著性差异(P<0.05),流速对Ka值影响显著,P<0.0001,相关系数为0.925。抑制P-糖蛋白(P-gp)后药物吸收速率未有明显变化。各剂量下胃吸收PRXT均较差(<5%)。结论在0.9～9.0mg·kg^-1内PRXT在大鼠肠道的吸收机制属于被动吸收,吸收过程服从一级动力学。P-gp对药物吸收没有影响。胃不是吸收的主要部位。循环流速对K_a影响较大,K_a随流速增大而增大。

Studies on Intestinal Absorption Kinetics of Paroxetine in Rats

OBJECTIVE To investigate the absorption kinetics of paroxetine hydrochloride (PRXT) at different segments of gastrointestinal tract under different dosages in rat.METHODS The absorption rate constant Ka of different segments under different dosages was evaluated by in situ recirculation model. The influence of circulation flow rate and P-glycoprotein(P-gp) on Ka was also tested.The concentrations of paronetine were detected by HPLC. RESULTS Ka from different segments was similar(P>0.05),and no distinctive effect on Ka was found (P>0.05). P-gp showed no significant effect (P>0.05) on absorption of PRXT.However, the flow rate showed a remarkable influence on absorption of PRXT (P<0.000 1), and with Pearson's correlation coefficient value as 0.925.The absorption of PRXT in stomach was comparatively poor (<5%).CONCLUSION The absorption of PRXT is a first-order process with a passive diffusion mechanism. PRXT is not the substrate of P-gp, and it is well absorbed in various intestinal tracts. Stomach is not the main area for PRXT absorption. Obviously, Ka is increased with the rising of flow rate.