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
Oral formulations of bisacodyl are only 16% bioavailable. A 10 mg enteric coated oral tablet reaches a Cmax of 26 ng/mL with a Tmax of 8 hours, while a 10 mg oral solution reaches a Cmax of 237 ng/mL with a Tmax of 1.7 hours. A 10 mg suppository reaches a Cmax of 0-64 ng/mL. In lactating women, 10mg of oral bisacodyl reaches a Cmax of 20.5-195 ng/mL, with a Tmax of 3-4 hours, and a geometric mean AUC after a single dose of 471 h\*ng/mL. After multiple doses, the geometric mean AUC decreases to 311 h\*ng/mL.
The majority of bisacodyl is eliminated in the feces. 13.8-17.0% of a bisacodyl dose is eliminated in the urine as the active metabolite BHPM.
Data regarding the volume of distribution of bisacodyl is not readily available. However, the volume of distribution of the active metabolite, BHPM, in lactating women is 181 L after a single dose and 289 L at steady state.
Data regarding the clearance of bisacodyl is not readily available. The apparent plasma clearance of the active metabolite, BHPM, in lactating women after a single 10 mg oral dose is 272 mL/min and after multiple doses is 412 mL/min.
Absorption of bisacodyl ... is minimal following oral or rectal administration. Any bisacodyl that is absorbed is metabolized in the liver and excreted in the urine and/or distributed in milk.
Following oral administration of therapeutic dosages of diphenylmethane derivatives, /bowel/ evacuation is produced in 6 to 8 hours. Rectally administered bisacodyl ... produces evacuation of the colon in within 15 minutes to 1 hour.
As much as 5% of orally administered dose is absorbed & excreted in urine as glucuronide.
Excreted primarily in the feces ...
The absorption and plasma level profile and laxative effects of 10 mg bisacodyl as an experimental solution ... in 12 healthy volunteers are described. Results indicate only small amounts of drug were systemically available after administration of /solution/, dragee /(sugar coated capsule)/ and suppository. Urinary excretion was 43.4% for solution, 9.2% for dragee and 3.1% for suppository.

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Metabolism / Metabolites
Bisacodyl is deacetylated to the active bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM) by an intestinal deacetylase. A small amount of BHPM is absorbed from the gastrointestinal tract, and is glucuronidated before elimination.
Following oral or rectal administration bisacodyl is converted to the active desacetyl metabolite bis(p-hydroxyphenyl)pyridyl-2-methane by intestinal and bacterial enzymes.
HPLC method which permits simultaneous detection of bisacodyl (BIS) & its monodesacetylated (mono) as well as totally desacetylated (DES) form, was used to study the intestinal handling of BIS (20 nmol/mL), when incubated for 60 min at the mucosal side of the preparations specified. In jejunal mucosa fluid, BIS disappeared completely in short time, & there was nearly equivalent rise in DES; mono was transitorily 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, & all 3 forms were present during incubation. It seemed still lower in mucosal fluid which had been in contact with colonic sac for 5 min. BIS & DES accumulate in jejunal & colonic serosal fluid mainly as conjugates (above 95%), & DES was in all cases the only conjugated metabolite present. Accumulation in jejunal serosal fluid was same whether BIS or DES was added.

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Biological Half-Life
Data regarding the half life of bisacodyl is not readily available. The half life of the active metabolite, BHPM, in lactating women was 7.3 h after a single 10 mg oral dose and 10.0 h after multiple doses.

Hepatotoxicity
Bisacodyl has not been associated with serum enzyme elevations during therapy or with instances of clinically apparent liver injury.
Likelihood score: E (unlikely cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Bisacodyl is not absorbed from the gastrointestinal tract, and its active metabolite, which is absorbed, is not detectable in breastmilk. Bisacodyl can be taken during breastfeeding and no special precautions are required.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Interactions
Milk, antacids, and histamine H2-receptor antagonist such as cimetidine, famotidine, nizatidine or ranitidine may cause the enteric coating to dissolve too rapidly, resulting in gastric or duodenal irritation when administered within one hour of bisacodyl tablets.
Chronic use or over use of laxatives may reduce serum potassium concentrations by by promoting excessive potassium loss from the intestinal tract; may interfer with potassium-retaining effects of potassium sparing diuretics.
In rat colon in situ bisacodyl stimulated biosynthesis of prostaglandin E (PGE). Inhibition of prostaglandin biosynthesis by pretreatment with indomethacin decreased effect of diphenolic laxatives.
Bisacodyl inhibited gastric emptying & motility in rats by activating reflex arising from small intestine. This effect was not prevented by alpha- or beta-sympatholytic, or by parasympatholytic agents. It was antagonized by quinine & quinidine, as well as by chloroquine & mepacrine. Inhibition of gastric motility by cathartics does not appear to be due to an effect on adrenergic or cholinergic pathways but rather involves a purinergic mechanism.

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Non-Human Toxicity Values
LD50 Dog oral >15 g/kg
LD50 Mouse oral 17.5 g/kg
LD50 Rat oral 4.3 g/kg
LD50 Rat oral >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
Cathartics
Oral bulk-forming, lubricant, and stool softener laxatives are indicated prophylactically in patients who should not strain during defecation, such as those with an episiotomy wound, painful thrombosed hemorrhoids, fissures or perianal abscesses, body wall and diaphragmatic hernias , anorectal stenosis, or postmyocardial infarction. /Laxatives; Included in US product labeling/
Oral laxatives are indicated for the short-term relief of constipation. Oral bulk-forming laxatives, stimulant laxatives, and carbon dioxide-releasing suppositories are indicated to facilitate defecation in geriatric patients with diminished colonic motor response... /Laxatives; Included in US product labeling/
Bisacodyl is useful as a laxative for the occasional relief of constipation and in bowel cleansing preparation for x-ray or endoscopic examination. Bisacodyl may be used as a laxative in postoperative, antepartum, or postpartum care or in preparation for delivery
In severe cases of constipation, such as with fecal impaction, mineral oil and stool softener laxatives administered orally or rectally are indicated to soften the impacted feces. To help complete the evacuation of the impacted colon, a rectal stimulant or saline laxative may follow. /Laxatives; Included in US product labeling/

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Drug Warnings
In therapeutic oral doses, all stimulant laxatives may produce some degree of abdominal discomfort, nausea, mild cramps, griping, and/or faintness. Rectal administration of bisacodyl suspensions ... may cause irritation and a sensation of burning of the rectal mucosa and mild proctitis. /Stimulant laxatives/
Weakness, incoordination, and orthostatic hypotension may be exacerbated in elderly patients as a result of significant electrolyte loss when stimulant laxatives are used repeatedly to evacuate the colon. /Stimulant laxatives/
Bisacodyl enteric-coated tablets are not recommenced for children up to 6 years of age since patients in this age group may have difficulty swallowing the tablet without chewing it. Gastric irritation may develop if the enteric coating is destroyed by chewing.
Laxatives should not be given to young children unless prescribed by a physician. Since children are not usually able to describe their symptoms precisely, proper diagnosis should precede the use of laxatives. This will avoid the complication of an existing condition (eg appendicitis) or the appearance of more severe side effects. /Laxatives/
For more Drug Warnings (Complete) data for BISACODYL (12 total), please visit the HSDB record page.

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Pharmacodynamics
Patients should be counselled regarding abdominal pain, nausea, vomiting, or a change in bowel function that lasts longer than 2 weeks. It has a wide therapeutic index, as patients can take 5-15 mg orally. Patients taking bisacodyl should be counselled before taking the medication if they are already experiencing abdominal pain, nausea, vomiting, or a change in bowel function lasting longer than 2 weeks. Patients should also be counselled to stop taking the medication if they experience rectal bleeding or no bowel movement in 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.)