Experimental Study of the Efficacy and Safety of a New PEG-Based Laxative

Bowel-cleansing PEG-based agents, including Moviprep^®, are commonly used to prepare the large intestine for diagnostic examinations. PLNV-next is a newly developed fixed combination medicinal product with a composition similar to that of Moviprep^®.

The aim of the study was to estimate the pharmacological efficacy and toxicity of PLNV-next.

Materials and methods: The study evaluated pharmacological efficacy of four formulations of PLNV-next in comparison with Moviprep^® after a single administration in a therapeutic dose to outbred rats. The evaluation was carried out based on the laxative effect of the medicinal products. The authors recorded diarrhoea onset latency and the number of defecation boluses and diarrhoea spots produced during the 6-hour observation period. Toxicity of PLNV-next was studied in the formulation containing maximum amounts of the ingredients according to the patent. In the single-dose toxicity study, PLNV-next was administered intragastrically to rats at doses of 4.2 g/kg (maximum human therapeutic dose, MHTD), 21 g/kg (5 MHTD), and 42 g/kg (10 MHTD) and to ferrets at doses of 4.2 g/kg (MHTD) and 21 g/kg (5 MHTD). In the repeated-dose toxicity study, PLNV-next was administered for 14 days at 4.2 g/kg (rats and ferrets), 21 g/kg (5 MHTD, rats), and 12.6 g/kg (3 MHTD, ferrets). Additionally, the repeated-dose toxicity study evaluated safety pharmacology parameters for the cardio-vascular, respiratory and central nervous systems.

Results: All PLNV-next formulations tested exerted a laxative effect equivalent to that of Moviprep^®. No clinical signs of toxicity were observed in rats, with the exception of the laxative effect. Ferrets demonstrated decreased behavioral activity and diarrhoea. Nausea or emesis were noted in 75–90% of the ferrets receiving the doses exceeding the MHTD. A single administration of PLNV-next affected blood sodium concentrations: a slight increase was noted in the 5 MHTD and 10 MHTD groups of rats and in the 5 MHTD group of ferrets. The repeated-dose toxicity study in rats revealed a slight increase in sodium levels with both test doses. After a single administration of 5 MHTD to ferrets, the authors observed a decrease in potassium levels. All the changes were mild and within physiological ranges. PLNV-next toxic effects observed in the rat and ferret studies were similar to those reported in rat and dog toxicity studies of Moviprep^®. 

Conclusion: PLNV-next exerts a marked laxative effect and has a favourable safety profile.

1. Connor A, Tolan D, Hughes S, Carr N, Tomson C. Consensus guidelines for the safe prescription and administration of oral bowelcleansing agents. Gut. 2012;61(11):1525–32. https://doi.org/10.1136/gutjnl-2011-300861

2. Davis GR, Santa Ana CA, Morawski SG, Fordtran JS. Development of a lavage solution associated with minimal water and electrolyte absorption or secretion. Gastroenterology. 1980;78(5):991–5. https://doi.org/10.1016/0016-5085(80)90781-7

3. Vanner SJ, MacDonald PH, Paterson WG, Prentice RS, Da Costa LR, Beck IT. A randomized prospective trial comparing oral sodium phosphate with standard polyethylene glycol-based lavage solution (Golytely) in the preparation of patients for colonoscopy. Am J Gastroenterol. 1990;85(4):422–7. PMID: 2183591

4. Sharara AI, Daroub H, Georges C, Shayto R, Nader R, Chalhoub J, Olabi A. Sensory characterization of bowel cleansing solutions. World J Gastrointest Endosc. 2016;8(15):508–16. https://doi.org/10.4253/wjge.v8.i15.508

5. Harrison NM, Hjelkrem MC. Bowel cleansing before colonoscopy: Balancing efficacy, safety, cost and patient tolerance. World J Gastrointest Endosc. 2016;8(1):4–12. https://doi.org/10.4253/wjge.v8.i1.4

6. Barkun AN, Martel M, Epstein IL, Hallé P, Hilsden RJ, James PD, et al. The Bowel CLEANsing National Initiative: a low-volume same-day polyethylene glycol (PEG) preparation vs low-volume split-dose PEG with bisacodyl or high-volume splitdose PEG preparations — a randomized controlled trial. Am J Gastroenterol. 2020;115(12):2068–76. https://doi.org/10.14309/ajg.0000000000000760

7. Spadaccini M, Frazzoni L, Vanella G, East J, Radaelli F, Spada C, et al. Efficacy and tolerability of high- vs low-volume split-dose bowel cleansing regimens for colonoscopy: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2020;18(7):1454–65. https://doi.org/10.1016/j.cgh.2019.10.044

8. Sharma P, Burke CA, Johnson DA, Cash BD. The importance of colonoscopy bowel preparation for the detection of colorectal lesions and colorectal cancer prevention. Endosc Int Open. 2020;8(5):E673–83. https://doi.org/10.1055/a-1127-3144

9. Zhang S, Zheng D, Wang J, Wu J, Lei P, Luo Q, et al. Simethicone improves bowel cleansing with low-volume polyethylene glycol: a multicenter randomized trial. Endoscopy. 2018;50(4):412–22. https://doi.org/10.1055/s-0043-121337

10. Tajika M, Tanaka T, Ishihara M, Hirayama Y, Oonishi S, Mizuno N, et al. Optimal intake of clear liquids during preparation for afternoon colonoscopy with low-volume polyethylene glycol plus ascorbic acid. Endosc Int Open. 2017;5(6):E416–23. https://doi.org/10.1055/s-0043-106185

11. Ponchon T, Boustière C, Heresbach D, Hagege H, Tarrerias AL, Halphen M. A low-volume polyethylene glycol plus ascorbate solution for bowel cleans ing prior to colonoscopy: the NORMO randomised clinical trial. Dig Liver Dis. 2013;45(10):820–6. https://doi.org/10.1016/j.dld.2013.04.009

12. Sagawa T, Sato K, Tomizawa T, Mizuide M, Yasuoka H, Shimoyama Y, et al. A prospective randomized controlled trial of AJG522 versus standard PEG+E as bowel preparation for colonoscopy. Biomed Res Int. 2015;2015:521756. https://doi.org/10.1155/2015/521756

13. Soh JS, Kim KJ. Combination could be another tool for bowel preparation? World J Gastroenterol. 2016;22(10):2915–21. https://doi.org/10.3748/wjg.v22.i10.2915

14. Shin SY, Ga KS, Kim IY, Park YM, Jung DH, Kim JH, et al. Predictive factors for inadequate bowel preparation using low-volume polyethylene glycol (PEG) plus ascorbic acid for an outpatient colonoscopy. Sci Rep. 2019;9(1):19715. https://doi.org/10.1038/s41598-019-56107-5

15. Corporaal S, Kleibeuker JH, Koornstra JJ. Low-volume PEG plus ascorbic acid versus high-volume PEG as bowel preparation for colonoscopy. Scand J Gastroenterol. 2010;45(11):1380–6. https://doi.org/10.3109/00365521003734158

16. Kelly NM, Rodgers C, Patterson N, Jacob SG, Mainie I. A prospective audit of the efficacy, safety, and acceptability of low-volume polyethylene glycol (2 L) versus standard volume polyethylene glycol (4 L) versus magnesium citrate plus stimulant laxative as bowel preparation for colonoscopy. J Clin Gastroenterol. 2012;46(7):595–601. https://doi.org/10.1097/MCG.0b013e3182432162

17. Balabanyan VYu, Fazylov MF, Nesteruk VV. Method for intestine cleansing and kit for its implementation. Patent of the Russian Federation No. 2709495; 2019 (In Russ.)

18. Poshivalov VP. Pharmacoethology. Saint-Petersburg: Copy-Service; 1997 (In Russ.)

19. Irwin S. Comprehensive observational assessment: Ia. A systematic, quantitative procedure for assessing the behavioral and physiologic state of the mouse. Psychopharmacologia. 1968;13(3):222–57. https://doi.org/10.1007/bf00401402

20. Gushchin YA, Muzhikyan AA. Effect of fixing liquids on microscopic structure of small laboratory animals. Mezhdunarodnyj vestnik veterinarii = International Bulletin of Veterinary Medicine. 2014;(3):88–95 (In Russ.)

21. Muzhikyan AA, Makarova MN, Gushchin YA. Features of histological processing of organs and tissues of laboratory animals. Mezhdunarodny vestnik veterinarii = International Bulletin of Veterinary Medicine. 2014;(2):103–9 (In Russ.)

22. Seow-En I, Seow-Choen F. A prospective randomized trial on the use of Coca-Cola Zero(®) vs water for polyethylene glycol bowel preparation before colonoscopy. Colorectal Dis. 2016;18(7):717–23. https://doi.org/10.1111/codi.13243

23. Heatley JJ, Russell KE. Exotic animal laboratory diagnosis. John Wiley & Sons; 2020. https://doi.org/10.1002/9781119108610

24. Lugovik IA, Makarova MN. Toxicological studies. Reference intervals of mass coefficients of internal organs in a sample of 1000 rats. Laboratornye zhivotnye dlya nauchykh issledovaniy = Laboratory Animals for Science. 2021;(1):3–11 (In Russ)] https://doi.org/10.29296/2618723X-2021-01-01

25. Huynh M, Laloi F. Diagnosis of liver disease in domestic ferrets (Mustela putorius). Vet Clin North Am Exot Anim Pract. 2013;16(1):121–44. https://doi.org/10.1016/j.cvex.2012.10.003