In the colon of rats, bisacodyl (20 mg/kg) increased TNF-α mRNA expression levels and decreased AQP3 protein expression [1]. In the range of 0.05 mg to 2.0 mg per 100 mL, bisacodyl decreases water absorption in the ileum, colon, and jejunum of rats. The degree of inhibition is linearly correlated with the logarithm of bisacodyl concentration [2]. Rat jejunum NOS activity can be significantly reduced by bisacodyl (10 mg/kg, gavage). The intragastric injection of bisacodyl (10 mg/kg) results in an increase in the markers' travel distance across all time periods [3]. When compared to rats given saline treatment, bisacodyl (5.9 mg/kg) dramatically decreased the activity of the colonic and jejunal (Na + K) ATPase. Without changing the amount of cAMP, bisacodyl (5.9 mg/kg) dramatically raised the PGE2 concentration in the colon and jejunum and boosted the activity of adenylyl cyclase in both organs when compared to control rats [4]. Rats treated with AOM and bisacodyl (4.3 mg/kg) had more crypts per lesion but fewer tumors overall. In rats, bisacodyl (43 mg/kg) dramatically increases the number of tumors and crypts per lesion [5].

Absorption, Distribution and Excretion
The bioavailability of bisacodyl oral formulations is only 16%. The peak plasma concentration (Cmax) of 10 mg enteric-coated tablets is 26 ng/mL, with a time to peak concentration (Tmax) of 8 hours; the Cmax of 10 mg oral solution is 237 ng/mL, with a Tmax of 1.7 hours. The Cmax of 10 mg suppositories ranges from 0 to 64 ng/mL. In lactating women, after oral administration of 10 mg bisacodyl, the Cmax range is 20.5–195 ng/mL, with a Tmax of 3–4 hours, and the geometric mean area under the curve (AUC) after a single dose is 471 hours ng/mL. After multiple doses, the AUC decreases to 311 hours ng/mL. Most bisacodyl is excreted in feces. 13.8%–17.0% of the dose of bisacodyl is excreted in the urine as the active metabolite BHPM. Data regarding the volume of distribution of bisacodyl are not available. However, in lactating women, the volume of distribution of the active metabolite BHPM is 181 L after a single dose and 289 L at steady state. Data regarding the clearance of bisacodyl are not available. In lactating women, the apparent plasma clearance of the active metabolite BHPM is 272 mL/min after a single oral dose of 10 mg bisacodyl and 412 mL/min after multiple doses. Bisacodyl absorption is minimal after oral or rectal administration. Any absorbed bisacodyl is metabolized in the liver and excreted in the urine and/or breast milk. Following oral administration of a therapeutic dose of a diphenylmethane derivative, defecation may occur within 6 to 8 hours. Rectal administration of bisacodyl may induce defecation in the colon within 15 minutes to 1 hour.
5% of the oral dose is absorbed and excreted in the urine as glucuronide.
Primarily excreted in the feces…
This article describes the absorption, plasma concentration curves, and laxative effect of 10 mg bisacodyl solution (experimental solution) in 12 healthy volunteers. Results showed that only small amounts of the drug entered the body after administration of the solution, sugar-coated capsules, and suppositories. The urinary excretion rate was 43.4% for the solution, 9.2% for the sugar-coated tablets, and 3.1% for the suppositories.
Metabolism/Metabolites

Bisacodyl is deacetylated by intestinal deacetylases to the active ingredient bis-(p-hydroxyphenyl)-pyridine-2-methane (BHPM). A small amount of BHPM is absorbed through the gastrointestinal tract and glucuronidated before excretion.
After oral or rectal administration, bisacodyl is converted to the active deacetylated metabolite bis-(p-hydroxyphenyl)-pyridine-2-methane by intestinal and bacterial enzymes.
High-performance liquid chromatography (HPLC) was used to simultaneously detect bisacodyl (BIS) and its mono- and deacetylated (DES) forms. The intestinal metabolism of BIS (20 nmol/mL) after 60 minutes of mucosal incubation with a specific formulation was investigated. In jejunal mucosal fluid, BIS disappeared completely within a short time, with DES at a nearly equivalent concentration; the mono-deacetylated product was transiently present. Hydrolysis was also rapid in mucosal fluid after 30 seconds of contact with the jejunal sac, but BIS was stable during blank incubation. The hydrolysis rate of BIS in the colonic sac was slower than in the jejunal sac, and all three forms of BIS were present during incubation. The hydrolysis rate of BIS appeared to be even lower in mucosal fluid after 5 minutes of contact with the colonic sac. BIS and DES accumulated primarily as conjugates (over 95%) in the jejunal and colonic serosal fluids, and in all cases, DES was the only conjugate metabolite present. The accumulation in the jejunal serosal fluid was the same regardless of the addition of either BIS or DES.

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Biological Half-Life
Data regarding the half-life of bisacodyl are not yet clear. In lactating women, the half-life of the active metabolite BHPM is 7.3 hours after a single oral dose of 10 mg; after multiple oral doses, the half-life is 10.0 hours.

Hepatotoxicity
Bisacodyl did not cause elevated serum enzymes or clinically visible liver injury during treatment. Probability score: E (unlikely to cause clinically visible liver injury). Pregnancy and Lactation Effects ◉ Overview of Use During Lactation Bisacodyl is not absorbed from the gastrointestinal tract, and its absorbable active metabolites are undetectable in breast milk. Lactating women can take bisacodyl without special precautions. ◉ Effects on Breastfed Infants No published information was found as of the revision date. ◉ Effects on Lactation and Breast Milk No published information was found as of the revision date.

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Interactions
Milk, antacids, and histamine H2 receptor antagonists (such as cimetidine, famotidine, nizatidine, or ranitidine) may cause excessively rapid dissolution of enteric coatings, potentially causing gastric or duodenal irritation if taken within one hour of taking bisacodyl tablets.
Prolonged or excessive use of laxatives may promote excessive intestinal potassium loss, thereby reducing serum potassium levels; it may also interfere with the potassium-sparing effects of potassium-sparing diuretics.
In the orthotopic rat colon, bisacodyl stimulates the biosynthesis of prostaglandin E (PGE). Indomethacin pretreatment inhibits prostaglandin biosynthesis, thereby reducing the effects of diphenol laxatives.
Bissacide inhibits gastric emptying and gastric motility in rats by activating a small intestinal reflex. This effect cannot be blocked by α- or β-sympathetic blockers or parasympathetic blockers. Quinine and quinidine, as well as chloroquine and mepacarin, can antagonize this effect. The inhibitory effect of laxatives on gastric motility does not appear to be due to influence on adrenergic or cholinergic pathways, but rather involves a purinergic mechanism.

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Non-human toxicity values
Dog oral LD50 >15 g/kg
Mouse oral LD50 17.5 g/kg
Rats oral LD50 4.3 g/kg
Rats oral LD50 >3 g/kg

[1]. The laxative effect of bisacodyl is attributable to decreased aquaporin-3 expression in the colon induced by increased PGE2 secretion from macrophages. Am J Physiol Gastrointest Liver Physiol, 2011. 301(5): p. G887-95.

[2]. Effect of bisacodyl on the structure and function of rodent and human intestine. Gastroenterology, 1977. 72(5 Pt 1): p. 849-56.

[3]. Karmeli, F., R. Stalnikowicz, and D. Rachmilewitz, Effect of colchicine and bisacodyl on rat intestinal transit and nitric oxide synthase activity. Scand J Gastroenterol, 1997. 32(8): p. 791-6.

[4]. Rachmilewitz, D., F. Karmeli, and E. Okon, Effects of bisacodyl on cAMP and prostaglandin E2 contents, (Na + K) ATPase, adenyl cyclase, and phosphodiesterase activities of rat intestine. Dig Dis Sci, 1980. 25(8): p. 602-8.

[5]. Effect of bisacodyl and cascara on growth of aberrant crypt foci and malignant tumors in the rat colon. Life Sci, 2001. 69(16): p. 1871-7.

Therapeutic Uses

Laxatives
Oral bulk-forming laxatives, lubricating laxatives, and stool softeners are indicated for patients who cannot strain during defecation, such as those with post-episiotomy wounds, painful thrombosed hemorrhoids, anal fissures or perianal abscesses, abdominal wall hernias and diaphragmatic hernias, anorectal stenosis, or post-myocardial infarction. They can also be used as a preventative measure. /Laxatives; included on the US product label/
Oral laxatives are indicated for short-term relief of constipation. Oral bulk-forming laxatives, stimulant laxatives, and carbon dioxide-releasing suppositories are indicated for assisting defecation in elderly patients with diminished colonic motility… /Laxatives; included on the US product label/
Bisacodone can be used as a laxative to relieve occasional constipation and for bowel preparation before X-rays or endoscopy. Bisacodyl can also be used for postoperative, prenatal, or postpartum care, or preparation for delivery.
For severe constipation, such as fecal impaction, oral or rectal administration of mineral oil and stool softeners is recommended to soften the impacted stool. To help completely clear the impacted colon, a rectal stimulant or saline laxative may be used afterwards. /Laxatives; US product label contains/

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Drug Warnings
At therapeutic doses, all stimulant laxatives may cause some degree of abdominal discomfort, nausea, mild cramps, abdominal pain, and/or syncope. Rectal administration of bisacodyl suspension…may cause rectal mucosal irritation and burning sensation, as well as mild proctitis. /Stimulant Laxatives/
Repeated use of stimulant laxatives in elderly patients may exacerbate weakness, incoordination, and orthostatic hypotension due to significant electrolyte loss. /Stimulant Laxatives/
Bisacodyl enteric-coated tablets are not recommended for children under 6 years of age, as children in this age may have difficulty swallowing the tablets and may need to chew them. Chewing may break the enteric coating and cause stomach irritation.
Laxatives should not be given to young children unless prescribed by a doctor. Because children often cannot accurately describe their symptoms, a proper diagnosis should be made before using laxatives. This will avoid exacerbating existing conditions (such as appendicitis) or causing more serious side effects. /Laxative/
For more complete data on drug warnings for bisacodyl (12 of them), please visit the HSDB record page.

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Pharmacodynamics
Patients should be informed of abdominal pain, nausea, vomiting, or changes in bowel habits lasting more than 2 weeks. Bisacodyl has a broad therapeutic index and can be taken orally in doses of 5-15 mg. If a patient has experienced abdominal pain, nausea, vomiting, or changes in bowel habits lasting more than 2 weeks before taking bisacodyl, they should be informed whether they need to take the medication. Patients should also be advised to discontinue the medication if they experience rectal bleeding or have not had a bowel movement within 12 hours.

C22H19NO4

361.3906

361.131

603-50-9

2391

White to off-white solid powder

1.2 g/cm3

492ºC

131 - 135ºC

4.112

0

5

7

27

457

0

KHOITXIGCFIULA-UHFFFAOYSA-N

InChI=1S/C22H19NO4/c1-15(24)26-19-10-6-17(7-11-19)22(21-5-3-4-14-23-21)18-8-12-20(13-9-18)27-16(2)25/h3-14,22H,1-2H3

[4-[(4-acetyloxyphenyl)-pyridin-2-ylmethyl]phenyl] acetate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~50 mg/mL (~138.35 mM)
H2O : ~0.1 mg/mL (~0.28 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.92 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (6.92 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (6.92 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)