Lumen perfusion of the human rectum in situ: a method to study mechanisms for rectal drug transport in humans.

A lumen perfusion system was developed to study rectal transport mechanisms in humans. With this technique it is possible to perfuse a well-defined area of the rectum wall under single-pass and recirculation conditions. Sodium benzoate was used as a test drug. After absorption, sodium benzoate is conjugated with glycine to give hippuric acid which is rapidly eliminated (t 1/2 = 0.5 h). Due to the short half-life it is possible to reach a steady-state concentration within 2.5 h of perfusion. Plasma concentrations of hippuric acid were determined by HPLC. The absorption influx of sodium benzoate per unit area (phi in) could be calculated using the steady-state concentration of hippuric acid during rectal perfusion, the separately measured total body clearance after intravenous injection, and a designated absorption surface of the rectum. It was shown that with this technique reproducible phi in values within one subject could be obtained. Four volunteers were perfused with four different solutions of sodium benzoate, and it was found that phi in was proportional to the four concentrations used. In the case of recirculation perfusion (two volunteers), it was found that the amount of the perfusate lost equalled the amount absorbed into the general circulation. Therefore, the possibility of major drug accumulation in the rectal lumen or mucosa could be excluded. The perfusion technique elaborated in the present study can be used to investigate the mechanism of rectal absorption in humans as well as the factors that may influence this process.