Picoprep Mechanism of Action

Pharmacotherapeutic group: Contact Laxatives. ATC code: A06A B58.
Pharmacology: Pharmacodynamics: Mechanism of action: Sodium picosulfate is hydrolyzed by colonic bacteria to form an active metabolite: bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM), which acts directly on the colonic mucosa to stimulate colonic peristalsis.
Magnesium oxide and citric acid react to create magnesium citrate in solution, which is an osmotic agent that causes water to be retained within the gastrointestinal tract.
Pharmacodynamic effects: The stimulant laxative activity of sodium picosulfate together with the osmotic laxative activity of magnesium citrate produces a purgative effect which, when ingested with additional fluids, produces watery diarrhea that clear the bowel.
The product is not intended for use as a routine laxative.
Pharmacokinetics: Absorption: Sodium picosulfate, which is a prodrug, is converted to its active metabolite, BHPM, by colonic bacteria.
After administration of 2 sachets of PICOPREP separated by 6 hours, in 16 healthy subjects, sodium picosulfate reached a mean Cmax of 3.2 ng/mL at a median 8 hours (Tmax). After the first sachet, the corresponding value was 2.3 ng/mL at 2 hours. Magnesium oxide and citric acid react in solution to create magnesium citrate. Magnesium concentration value not corrected for baseline were 0.88 and 0.95 mmol/L at 4 and 10 hours, respectively. The baseline value was 0.75 mmol/L.
Distribution: The apparent volume (V/F) of sodium picosulfate was 3910 liters.
Biotransformation and Elimination: The fraction of the sodium picosulfate dose excreted unchanged in urine was 0.11%. Plasma levels of BHPM were low with 13 out of 16 subjects studied having plasma BHPM concentrations below the lower limit of quantification (0.1 ng/mL). Urinary samples show that the majority of excreted BHPM was in the glucuronide-conjugated form. The apparent clearance (CL/F) of sodium picosulfate was 463 L/h. The terminal half-life of sodium picosulfate was 7.4 hours.
Clinical studies in bowel cleansing before colonoscopy have shown an increase from baseline to colonoscopy visit in serum magnesium of approximately 0.11 mmol/L (from 0.86 to 0.97 mmol/L). All changes in serum magnesium were transient and within normal limits, including in patients with mild to moderate renal impairment.
Toxicology: Preclinical safety data: Non-clinical data reveal no special hazard for humans based on conventional studies of repeated dose toxicity and genotoxicity.
Due to the very short treatment duration no long-term studies in animals have been performed.
Reproductive studies have shown no potential for impairment of fertility or harm to the foetus for sodium picosulfate and PICOPREP.
In an animal study on pre- and postnatal development, the NOAEL of PICOPREP was the mid dose of 750 mg/kg BID. The adverse effect that occurred in the 2000 mg/kg BID group (approximately 8 times the recommended human dose), was pup mortality, between lactation days 2 to 4 due to maternal toxicity.
Effects in reproductive and developmental toxicity studies in animals with sodium picosulfate alone were observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use.