Effect of water-loading on the performance of polyethylene glycol as a marker of small intestinal permeability

1. Polyethylene glycol has been used extensively to measure small intestinal permeability in vivo. However, polyethylene glycol seems to traverse the intestinal mucosa in much greater quantities than sugar molecules of equivalent M(r). In addition, the recovery of the lowest M(r) polymers of administered polyethylene glycol has been found to be both low and unreliable. 2. To compare the behaviour of a range of polyethylene glycol polymers with sugar probes in vivo, a combined polyethylene glycol/mannitol/lactulose probe was administered sequentially to healthy individuals in the fasted state and under conditions of water-loading. Timed hourly urine collections were made for 6 h. 3. Mannitol and lactulose recoveries were all within the normal range and were unaffected by co-administration of water. The lactulose/mannitol recovery ratios did not vary significantly over the 6 h collection period. In contrast, the recovery of total polyethylene glycol was significantly greater when subjects were water-loaded. Furthermore, proportionally greater quantities of polyethylene glycol M(r) 370 than M(r) 854 were recovered towards the end of the collection period than at the start. 4. Our results show that, in contrast to lactulose and mannitol, excretion of low-medium M(r) polyethylene glycol polymers is highly dependent on co-administration of water. Furthermore, the differential rate of excretion of the low compared with the high M(r) polyethylene glycol polymers suggests that the volume of distribution of the individual polymers may vary with M(r), and smaller polyethylene glycol molecules may undergo considerable renal tubular reabsorption.