SUMMARYBackground: Phenolphthalein is widely used as a safe and effective laxative. After oral administration, phenolphthalein is absorbed in the small bowel and is conjugated in the liver to phenolphthalein glucuronide which passes into the colon where it is deconjugated and the active compound, phenolphthalein, is released. Since phenolphthalein glucuronide does not undergo enterohepatic circulation it should theoretically have a more rapid onset of action and a lower threshold dose for taxation. The present study was designed to examine this issue.Methods: Ten normal healthy subjects volunteered for the study. All subjects were administered placebo, phenolphthalein (at doses of 15, 30, 45, 60, 75 and 90 mg) or phenolphthalein glucuronide (at equivalent doses of 24, 48, 72, 96, 120 and 144 mg) in a random order. Stool weight, the frequency and consistency of stools, and the development of symptoms were recorded at 12‐h intervals for 84 h.Results: There was a significant increase in the mean stool weight obtained within the first 24 h of administration of a 30 mg dose of phenolphthalein and its glucuronide equivalent compared to the values obtained with placebo. A further increase in the dose did not improve the therapeutic response. There was no difference between phenolphthalein and phenolphthalein glucuronide with respect to the rapidity of action, the threshold dose, effectiveness of taxation, or the frequency of adverse effects.Conclusions: The therapeutic response and side effect profile of the different doses favoured 30 mg phenolphthalein as the optimum laxative dose. Although theoretically superior, phenolphthalein glucuronide was not found to be a more effective laxative compared to phenolphthalein in normal subjects.
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