ビサコジル

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.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 85,000(SRC), determined from a structure estimation method(2), indicates that bisacodyl is expected to be immobile in soil(SRC). Volatilization of bisacodyl from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 7.3X10-12 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Bisacodyl is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.8X10-8 mm Hg(SRC), determined from a fragment constant method(4). Biodegradation data were not available(SRC, 2005).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 85,000(SRC), determined from a structure estimation method(2), indicates that bisacodyl is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 7.3X10-12 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). A base-catalyzed second-order hydrolysis rate constant of 2.3 L/mole-sec(SRC) was estimated using a structure estimation method(5); this corresponds to half-lives of 35 and 3.5 days at pH values of 7 and 8, respectively(5). According to a classification scheme(6), an estimated BCF of 78(SRC), from an estimated log Kow of 3.37(7) and a regression-derived equation(8), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Biodegradation data were not available(SRC, 2005).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), bisacodyl, which has an estimated vapor pressure of 4.8X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase bisacodyl may be removed from the air by wet and dry deposition(SRC). Bisacodyl does not absorb light at wavelengths >290 nm(3) and would not be expected to be susceptible to direct photolysis by sunlight(SRC).

The most common adverse effects, seen in more than 5% of patients taking bisacodyl, are diarrhea, abdominal pain (mainly in the upper abdomen), and headache. Although it is unlikely that chronic use of bisacodyl is harmful to the colon, it could induce abdominal discomfort and cramping pain. Joo JS et al summarized that 45% of patients using bisacodyl or other laxatives (phenolphthalein, senna, and casanthranol) more than 3 times per week for 1 year or longer had subsequent radiographic changes of colonic redundancy and dilation of the colon, with loss of haustral markings which did not occur in the control groups. These agents may cause a neuronal injury or damage colonic longitudinal musculature.

Using a structure estimation method based on molecular connectivity indices(1), the Koc for bisacodyl can be estimated to be 85,000(SRC). According to a classification scheme(2), this estimated Koc value suggests that bisacodyl is expected to be immobile in soil.

/SIGNS AND SYMPTOMS/ With long term use or overdosage of stimulant laxatives, electrolyte disturbances including hypokalemia, hypocalcemia, metabolic acidosis or alkalosis, abdominal pain, diarrhea, malabsorption, weight loss , and protein-losing enteropathy may occur Electrolyte disturbances may produce vomiting and muscle weakness; rarely osteomalacia, secondary aldosteronism, and tetany may occur. Pathologic changes in including structural damage to the myenteric plexus, severe and permanent interference with colonic motility, and hypertrophy of the muscularis mucosae may occur with chronic use. /Stimulant laxatives/

Drug Induced Liver Injury Rank (DILIrank 2.0)

Bisacodyl

vNo-DILI-concern

0

No match

DOI:10.1016/j.drudis.2016.02.015

An estimated BCF of 78 was calculated for bisacodyl(SRC), using an estimated log Kow of 3.37(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC), provided the compound is not altered physically or chemically once released into the environment(SRP).

The Henry's Law constant for bisacodyl is estimated as 7.3X10-12 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that bisacodyl is expected to be essentially nonvolatile from water surfaces(2). Bisacodyl's Henry's Law constant indicates that volatilization from moist soil surfaces should not occur(SRC). Bisacodyl is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.8X10-8 mm Hg(SRC), determined from a fragment constant method(3).

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Dietary supplementation with bisacodyl at concentrations ranging from 1 to 0.3% was found to induce both calculi and epithelial proliferation lesions, including a transitional-cell carcinoma, in the urinary bladder of F344uCrj rats. In order to clarify the relationship between the bisacodyl-associated urinary bladder calculi and the development of proliferative lesions in the urinary bladder, male and female rats were administered bisacodyl-diets at concentrations of 0.3, 0.1, and 0.03% for 32 wk. Both sexes of animals treated with bisacodyl suffered from diarrhea throughout the experimental period. Epithelial proliferative lesions and calculus formation were observed only in the urinary bladder of male rats given the 0.3% bisacodyl diet. Proliferative lesions and increases of bromouracil deoxyriboside (BUdR) labeling indices were found only in the urinary bladder epithelium of rats with calculi, the severity of the former correlating with the calculus weight ...

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl bisacodyl, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Cathartic

MEDICATION

Use (kg; approx.) in Germany (2009): >1000

(1977) No Data

(1979) No Data

(1978) 1.01X10+6 G (PRINCPL CUSTMS DISTS)

(1979) 1.94X10+6 G (PRINCPL CUSTMS DISTS)

(1977) PROBABLY GREATER THAN 4.54X10+5 GRAMS

(1978) PROBABLY GREATER THAN 4.54X10+5 GRAMS

Condensation of 2-pyridinecarboxaldehyde with phenol in the presence of sulfuric acid, followed by esterification with acetic anhydride and anhydrous sodium acetate

... Produced by condensation of 2-pyridinealdehyde with phenol in the presence of dehydrating compounds. Subsequently, the phenolic hydroxyl groups are acetylated.

Preparation: GB 730243; A. Kottler, E. Seeger, US 2764590 (1955,1956 both to Thomae).

Complex with tannin: Bisacodyl tannex; Clysodrast.

Bisacodyl is available in an enteric-coated preparation given once daily, the usual oral dose for which is 10 to 15 mg for adults and 5 to 10 mg for children 6 to 12 years old.

Bisacodyl Enema is supplied in a 1.25 fluid ounce (37 mL) ready-to-use squeeze bottle.

/Bisacodyl/ stimulant laxative tablets are supplied in cartons of 25 tablets (5 mg each tablet) wrapped in a foil seal.

Bisacodyl suppositories are supplied in cartons of 4 individually foil-wrapped suppositories.

Phenol, 4,4'-(2-pyridinylmethylene)bis-, 1,1'-diacetate: ACTIVE

Information available in 2005 indicated that Bisacodyl was used in the manufacture of pharmaceutical preparations in the following countries: Algeria, Antigua & Barbuda, Argentina, Aruba, Australia, Austria, Bahamas, Bahrain, Bangladesh, Barbados, Belgium, Bermuda, Brazil, Bulgaria, Canada, Cayman Islands, Chile, Colombia, Croatia, Cyprus, Czech Republic, Denmark, Ecuador, Egypt, Finland, France, Germany, Greece, Grenada, Guyana, Haiti, Hong Kong, Hungary, India, Indonesia, Ireland, Iraq, Israel, Italy, Jamaica, Japan, Jordan, Kenya, Kuwait, Lebanon, Libyan Arab Jamahiriya, Luxembourg, Malaysia, Malta, Mauritius, Mexico, Morocco, Netherlands, Netherlands Antilles, New Zealand, Nigeria, Norway, Oman, Poland, Portugal, Qatar, Romania, Russian Federation, Saint Lucia, Saint Vincent & The Grenadines, Saudi Arabia, Singapore, Slovenia, South Africa, Spain, Sweden, Switzerland, Sudan, Syrian Arab Republic, Thailand, Trinidad & Tobago, Tunisia, Turkey, United Arab Emirates, United Kingdom, United States, Yemen, Yugoslavia (1,2)