INTESTINAL DRUG ABSORPTION DURING INDUCED NET WATER-ABSORPTION IN MAN- A MECHANISTIC STUDY USING ANTIPYRINE, ATENOLOL AND ENALAPRILAT

1 The effect of induced water absorption on the intestinal permeabilit y of antipyrine, atenolol and enalaprilat in the proximal jejunum was studied in eight healthy subjects with a regional intestinal perfusion technique. 2 The mean (+/- s.d.) net water flux changed from a secret ory status of 1.2 +/- 1.2 ml h(-1) cm(-1) to an absorptive status of - 3.7 +/- 3.5 ml h(-1) cm(-1) (P < 0.0025) on the introduction of a hypo -osmolar glucose-containing electrolyte solution. 3 The mean permeabil ity values for the three drugs in the eight subjects were unchanged de spite the increase in net water absorption (5.7 +/- 3.0 to 7.0 +/- 3.6 x 10(-4) cm s(-1) for antipyrine, 0.1 +/- 0.2 to 0.2 +/- 0.2 x 10(-4) cm s(-1) for atenolol and 0.3 +/-0.3 to 0.1 +/- 0.2 x 10(-4) cm s(-1) for enalaprilat). One subject showed a large change in the permeabili ty for antipyrine and atenolol in parallel with a large increase in wa ter absorption, but enalaprilat was unaffected. 4 The luminal recovery of PEG 4000 was similar before (100 +/- 4%) and during (101 +/- 7%) i nduction of water absorption, which indicates that the barrier functio n of the intestine appears to be maintained during glucose-stimulated fluid absorption in man. 5 We conclude that induced net water absorpti on in man does not influence the paracellular permeability of hydrophi lic drugs or drugs with high molecular weight to any significant exten t. We suggest that this is because an important component of the net f lux of water across the epithelial membrane may be transcellular and, in addition, the increased net absorptive flow of water could be due t o a decreased secretory part of this flux.