THE EFFECTS OF ENPROSTIL AND RS-86505-007 ON INVITRO INTESTINAL PERMEABILITY OF RABBIT AND MONKEY

Abstract— Enprostil is a prostaglandin E2 analogue characterized as a racemic mixture of four stereoisomers. Enprostil and a single isomer, RS‐86505‐007, were evaluated for their effects on the permeability of actively and passively transported compounds in segments of small intestine from rabbits and monkeys. Consistent with human in‐vivo studies, which have demonstrated decreases in absorption of D‐xylose, both compounds inhibited D‐glucose transport. The passively transported compounds mannitol and progesterone were also less permeable in this model in the presence of enprostil or RS‐86505‐007. In contrast to the concentration‐dependent inhibition displayed by ouabain, RS‐86505‐007 had no effect on purifed Na+K+‐ATPase. It is suggested that an effect of a general nature, possibly an increase in the barrier properties at the intestinal surface, may explain the transport inhibition. Of two other enprostil isomers, RS‐86812‐007 inhibited D‐glucose transport in rabbit small intestine, while RS‐86505‐008 had no effect. The prostaglandin E1 analogue misoprostol was ineffective in monkey and poorly effective in rabbit. This suggests that the inhibition of D‐glucose transport by enprostil and its active stereoisomers is mediated through some structurally specific receptor interaction. 1990 Royal Pharmaceutical Society of Great Britain