Source: Health Products Regulatory Authority (IE) Revision Year: 2022 Publisher: Laboratoires Mayoly Spindler, 6 avenue de leurope BP 51, 78401 CHATOU Cedex, France
ATC code: A06AD15
Osmotically acting laxatives
High molecular weight macrogols are long linear polymers which retain water molecules by means of hydrogen bonds. When administered by the oral route, they lead to an increase in volume of intestinal fluids.
The volume of unabsorbed intestinal fluid accounts for the laxative properties of the solution.
Studies showed that MACROGOL is negligibly absorbed and predominantly eliminated via faeces (93% of the dose in one study).
In healthy adult volunteers after oral dosing with 17 g, MACROGOL 3350 was detected in plasma as early as 30 minutes, reached maximum levels (mean Cmax ranging from 353–1111 ng/ ml) within a mean of 2.0–5.4 hours and fell, in most subjects, to undetectable levels by 18–24 hours.
The half was variable with a range of 3.6 to 8 hours. The small amount of MACROGOL absorbed systemically is excreted in the urine. Excretion is prolonged with MACROGOL 3350 detected at 60 hours post dose in urine and 96 hours post dose in faeces. Patients with end stage renal disease (ESRD) have significantly higher exposure to MACROGOL 3350 than healthy adults. Orally administered MACROGOL 3350 is excreted primarily in faeces. Healthy adult volunteers clear absorbed MACROGOL 3350 rapidly via urinary excretion; these data suggest that, in the absence of renal function, PEG 3350 plasma levels are higher in ESRD patients and that the rate of clearance is slower. Dialysis may reduce MACROGOL 3350 levels but several dialysis sessions may be needed to clear PEG 3350 from plasma. The plasma level of PEG 3350 was similar 24 hours after 4, 6 or 7 daily doses, suggesting that PEG 3350 does not accumulate in plasma of ESRD patients dosed repeatedly for up to 7 days.
There were no adverse events associated with these levels of exposure in ESRD patients. Although the extent of exposure in ESRD patients was greater than in healthy adult volunteers, the Cmax was less than 1/10 those observed in rodents receiving daily oral doses of PEG for 6 months while the AUC(0-tau) was about 3 times lower.
Preclinical studies provide evidence that MACROGOL 3350 has no significant systemic toxicity potential, based on conventional studies of pharmacology, repeated dose toxicity and genotoxicity.
Reproductive and developmental studies conducted in rabbits and/or rats were negative for effects on reproductive performance, embryo-fetal development and changes in F1 generation up to a dose level that is a multiple of 7 x the maximum recommended dose in humans for the symptomatic treatment of chronic constipation.
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