Sodium picosulfate Other names: Sodium picosulphate

Sodium picosulfate is a locally acting laxative from the triarylmethane group, which after bacterial cleavage in the colon, has a dual-action with stimulation of the mucosa of both the large intestine and of the rectum. Stimulation of the mucosa of the large intestine results in colonic peristalsis, with promotion of accumulation of water, and consequently electrolytes, in the colonic lumen. This results in stimulation of defaecation, reduction of transit time and softening of the stool. Stimulation of the rectum causes increased motility and a feeling of rectal fullness. The rectal effect may help to restore the “call to stool” although its clinical relevance remains to be established.

As a laxative that acts on the colon, sodium picosulfate is ineffective in altering the digestion or absorption of calories or essential nutrients in the small intestine.

Absorption and Distribution

After oral ingestion, sodium picosulfate reaches the colon without any appreciable absorption. Therefore, enterohepatic circulation is avoided.

Biotransformation

Sodium picosulfate is converted into the active laxative compound, bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM), via bacterial cleavage in the distal segment of the intestine.

Elimination

Following conversion, only small amounts of BHPM are absorbed and are almost completely conjugated in the intestinal wall and the liver to form the inactive BHPM glucuronide. After oral administration of 10 mg sodium picosulfate 10.4% of the total dose was excreted as BHPM glucuronide in urine after 48 hours. In general, urinary excretion decreases when higher doses of sodium picosulfate are being administered.

Pharmacokinetic/Pharmacodynamic relationship(s)

Consequently, the onset of action of the preparation is usually between 6-12 hours, which is determined by the release of the active substance (BHPM). There is no direct or inverse relationship between the laxative effect and plasma levels of the active moiety.

Sodium picosulfate was maternotoxic (severe diarrhoea) in rats and rabbits at exposures ≥810 fold above the maximum recommended human daily dose [MRHDD] based on mg/m². Embryotoxicity (increased incidence of early resorptions) was observed at maternotoxic doses in rats and rabbits and was considered secondary to maternotoxicity. There were no other reported effects on embryofetal development, pre- and postnatal development and fertility parameters at exposures up to 81-fold above the MRHDD based on mg/m².