Magnesium hydroxide: new insights into the mechanism of its laxative effect and the potential involvement of prostaglandin E2.
The mechanism by which Mg(OH)2 acts as a laxative is unknown. To explore the mechanism, six volunteers more than 55 years old, with normal bowel habits, were enrolled in a dose-response, randomized, placebo-controlled, double-blind, crossover design study. Each subject was studied for four inpatient periods of 5 days each on a metabolic ward with 9 days off of all medication between studies. In the hospital, all patients were on a diet fixed in calories, fluid volume, Na+, fiber, and Ca2+. At 8 p.m. on each study day, each subject took 45 ml containing either placebo or 1,200, 2,400, or 3,600 mg of Mg(OH)2 plus 240 ml of water. On the fourth and fifth hospital days of each period, 24-h stool output was quantified and analyses performed. Compared to placebo, Mg(OH)2 caused the following dose-dependent results: (a) increased number of bowel movements; (b) increased percentage of stool water; (c) increased stool volume; (d) increased stool Mg2+; and (e) increased total stool 24-h prostaglandin E2 (PGE2), with mean 24-h excretions as follow: placebo, 95 +/- 18 pg/24 h; 1,200 mg Mg(OH)2, 260 +/- 100; 2,400 mg Mg(OH)2, 357 +/- 117; and 3,600 mg Mg(OH)2, 525 +/- 196. There was a significant correlation between stool PGE2 excretion and stool water consistent with a causative relationship. However, the concentration of stool prostaglandin was lower than the concentration found to alter intestinal electrolyte transport in vitro. In summary, the laxative effect of Mg(OH)2 is associated with increased output of stool PGE2. The contribution of the stool PGE2 to the laxative effect of Mg(OH)2 is unknown.
Donowitz
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M
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Rood
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D002400:Cathartics; D003672:Defecation / Q000187:drug effects; D015232:Dinoprostone / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005772:Gastrointestinal Transit / Q000187:drug effects; D006801:Humans; D008276:Magnesium Hydroxide / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D014882:Water-Electrolyte Balance / Q000187:drug effects
D002400:Cathartics; D015232:Dinoprostone; D008276:Magnesium Hydroxide