No abstract

The enterohepatic circulation of cefixime in rat was evaluated by a nonlinear least square analysis program, MULTI(FILT), into which the fast inverse Laplace transform (FILT) was incorporated. The plasma time course in the bile duct-cannulated rat exhibited a biexponential curve after the rapid iv administration of cefixime. Several pharmacokinetic models for the enterohepatic circulation were constructed based on the recirculatory concept and the Laplace-transformed equations corresponding to these models were derived by means of the method of transfer function. The transformed equations were simultaneously fitted to the time courses of plasma concentration in rats with laparotomy and with bile duct cannula. The optimum model was selected based on the Akaike's information criterion (AIC). The local moment characteristics for a single pass through enterohepatic circulation were further calculated from the time courses of both the plasma concentration and the amount excreted into the bile. The recovery ratio (Fc) and the mean circulatory time (-tc) through a single pass of enterohepatic circulation were estimated 27.9% and 1.07 hr, respectively. The recovery ratio (Fa) and the mean absorption time (-tc) for the absorption process from the intestinal tract into the systemic circulation were 68.3% and 0.0234 hr, respectively. The recovery ratio (Fb) and the mean transit time (-tb) for the disposition process through the systemic circulation into the bile were 40.8% and 1.05 hr, respectively.

α‐Amylase, which plays an essential role in starch degradation, is expressed mainly in the pancreas and salivary glands. Human α‐amylase is also detected in other tissues, but it is unclear whether the α‐amylase is endogenously expressed in each tissue or mixed exogenously with one expressed by the pancreas or salivary glands. Furthermore, the biological significance of these α‐amylases detected in tissues other than the pancreas and salivary glands has not been elucidated. We discovered that human α‐amylase is expressed in intestinal epithelial cells and analyzed the effects of suppressing α‐amylase expression. α‐Amylase was found to be expressed at the second‐highest messenger RNA level in the duodenum in human normal tissues after the pancreas. α‐Amylase was detected in the cell extract of Caco‐2 intestinal epithelial cells but not secreted into the culture medium. The amount of α‐amylase expressed increased depending on the length of the culture of Caco‐2 cells, suggesting that α‐amylase is expressed in small intestine epithelial cells rather than the colon because the cells differentiate spontaneously upon reaching confluence in culture to exhibit the characteristics of small intestinal epithelial cells rather than colon cells. The α‐amylase expressed in Caco‐2 cells had enzymatic activity and was identified as AMY2B, one of the two isoforms of pancreatic α‐amylase. The suppression of α‐amylase expression by small interfering RNA inhibited cell differentiation and proliferation. These results demonstrate for the first time that α‐amylase is expressed in human intestinal epithelial cells and affects cell proliferation and differentiation. This α‐amylase may induce the proliferation and differentiation of small intestine epithelial cells, supporting a rapid turnover of cells to maintain a healthy intestinal lumen.