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References: Laxative

Naunyn Schmiedebergs Arch Pharmacol. 1982 Nov;321(2):149-56.
Appearance of 14C-polyethylene glycol 4000 in intestinal venous blood: influence of osmolarity and laxatives, effect on net water flux determination.

Winne D, Gorig H.

In anaesthetized rats the appearance rate of 14C-polyethylene glycol 4000 (14C-PEG 4000) was measured in the intestinal venous blood after intraluminal administration into a jejunal, ileal, and colonic segment. The absorption rate was small, especially in the colon (0.5-4.2% within 60 min in an intestinal segment of about 300 mg wet tissue weight depending on the batch of 14C-PEG 4000). The absorbed PEG in the plasma consisted mainly of molecules with lower molecular weight than 4000 which were included in the commercial batches of 14C-PEG 4000. The appearance rate of 14C-PEG decreased with time after single dose but remained constant, when a 14C-PEG solution was perfused continuously through the intestinal lumen. A hypotonic solution increased and a hypertonic one decreased slightly the absorption of PEG in the jejunum and ileum but not in the colon. The influence of bisacodyl (100 mgl(-1)) and ricinoleate (10 mmol l(-1)) on the absorption of PEG was small or absent, while deoxycholate (5 mmol 1(-1)) raised the absorption rate considerably, predominantly of the high molecular weight fraction. If in intestinal absorption studies a batch of commercial 14C-PEG 4000 with a small low molecular weight fraction is used, the error in the determination of net water flux caused by the absorption of PEG can be neglected. The influence of osmolarity and laxatives is insignificant. Bile acids increase the intestinal permeability of PEG 4000, so that the net water flux determination can be biased considerably.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7155194&dopt=Abstract constipation laxative

Acta Pharmacol Toxicol (Copenh). 1982 Oct;51(4):388-94.
Intestinal handling of bisacodyl and picosulphate by everted sacs of the rat jejunum and stripped colon.

Hillestad B, Sund RB, Buajordet M.

Bisacodyl (BIS) is the acetic acid di-ester of the laxative diphenol 2-(4,4'-dihydroxydiphenyl)methyl-pyridine. A HPLC-method which permits the simultaneous determination of BIS and its monodesacetylated (MONO) as well as totally desacetylated (DES) form, has been used to study the intestinal handling of BIS (20 nmol/ml), when the compound was incubated for 60 min. at the mucosal side of the preparations specified. In the jejunal mucosal fluid, BIS disappeared completely in short time, and there was a nearly equivalent rise in DES. MONO was transitory present. Hydrolysis was also rapid in mucosal fluid which had been in contact with jejunal sacs for 30 sec., but BIS was stable in blank incubations. Hydrolysis of BIS was slower by colonic than by jejunal sacs, and all three molecular forms were present during incubation. It seemed still slower in mucosal fluid which had been in contact with colonic sacs for 5 min. BIS just as DES accumulated in the jejunal and colonic serosal fluid mainly as conjugates (greater than 95%), and DES was in all cases the only unconjugated metabolite present. Drug accumulation in jejunal serosal fluid was the same whether BIS or DES was added. However, more drug seemed to accumulate on the serosal side of colonic sacs when incubated with BIS instead of DES. In similar experiments with picosulphate, which is the sulphuric acid di-ester analogue of BIS, free DES was not detected in the mucosal fluid during incubation. The amounts of laxative accumulating in the serosal fluid were less than 1/10 of those observed with BIS.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7180502&dopt=Abstract constipation laxative

J Pharm Pharmacol. 1981 Aug;33(8):526-8.
Influence of 1,8-dihydroxyanthraquinone and loperamide on the paracellular permeability across colonic mucosa.

Verhaeren EH, Dreessen MJ, Lemli JA.

Administration of 1,8-dihydroxyanthraquinone (DHA) markedly increases the permeability of guinea-pig colonic mucosa. In 1 h 25% of the administered dose of 99mTc-EDTA complex leaks through the mucosa. Orally administered loperamide blocks the 99mTc-EDTA transfer after DHA administration. Loperamide injected in situ in the ligated colon segment shows the same blocking properties of the transfer rate of the complex. These findings suggest that the opposing action on fluid transport of the laxative DHA and the antidiarrhoeal loperamide could be due to these drugs affecting the permeability of the colonic mucosa. The minimal dose of loperamide, able to restore normal permeability, was as low as 0.01 mg kg-1.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6115928&dopt=Abstract constipation laxative

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