Dose dumping is a phenomenon of drug metabolism in which environmental factors can cause the premature and exaggerated release of a

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

. This can greatly increase the

concentration In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', '' molar concentration'', '' number concentration'', ...

of a drug in the body and thereby produce adverse effects or even drug-induced

toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacteria, bacterium, or plant, as well as the effect o ...

. Dose dumping is most commonly seen in drugs taken by mouth and digested in the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...

. Around the same time patients take their medication, they can also ingest other substances like fatty meals or

alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...

that increase

drug delivery Drug delivery involves various methods and technologies designed to transport pharmaceutical compounds to their target sites helping therapeutic effect. It involves principles related to drug preparation, route of administration, site-specif ...

. The substances may act on the drug's capsule to speed up drug release, or they may stimulate the body's absorptive surfaces to increase the rate of drug uptake. Dose dumping is a disadvantage found in extended release dosage form. In general, drug companies try to avoid drugs with significant dose dumping effects. Such drugs are prone to problems and are often pulled from the market. Such was the case with the

pain Pain is a distressing feeling often caused by intense or damaging Stimulus (physiology), stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sense, sensory and emotional experience associated with, or res ...

medication Palladone Once Daily formulation due to its dose-dumping effects when taken with alcohol.

Types of dose dumping

Alcohol-induced dose dumping (AIDD)

It is by definition an unintended rapid release in large amounts of a

modified-release dosage Modified-release dosage is a mechanism that (in contrast to immediate-release dosage) delivers a drug with a delay after its administration (delayed-release dosage) or for a prolonged period of time (extended-release R, XR, XLdosage) or to a spe ...

due to a co-ingestion with ethanol. Some interactions between alcohol, biological factors and the presentation of the drug can influence the apparition of AIDD by: * Disrupting the drug release mechanism. * Prolonging gastric emptying. * Changing the amount of gastric acid. * Enhancing the drug absorption due to an increase in

solubility In chemistry, solubility is the ability of a chemical substance, substance, the solute, to form a solution (chemistry), solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form su ...

. * Increasing the wetting effect and therefore speeding up the drug release. * A decrease in swelling capacity by the matrix, accelerating the release.

Food-induced dose dumping (FIDD)

Food intake produces dynamic changes in digestion and

pharmacokinetics Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to describing how the body affects a specific su ...

through a variety of mechanisms, which can produce an unintended release of modified-release dosages under certain circumstances. Usually, high fat diets are the most associated with this phenomenon, but there is evidence that standard-composition food can cause this even in immediate release formulations, such as the case of

methylphenidate Methylphenidate, sold under the brand names Ritalin ( ) and Concerta ( ) among others, is a central nervous system (CNS) stimulant used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It may be taken Oral adm ...

. Some of the mechanisms involved in FIDD are: * Changes in composition and volumes of luminal fluid. * Modification in gastrointestinal motility and consequently transit time of the stomach. * Variation in concentration of

bile Bile (from Latin ''bilis''), also known as gall, is a yellow-green/misty green fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is primarily composed of water, is pro ...

salts and

lipids Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins Vitamin A, A, Vitamin D, D, Vitamin E, E and Vitamin K, K), monoglycerides, diglycerides, phospholipids, and others. The fu ...

. * Loss of drug's matrix integrity due to changes in pH, fat and bile.

References

Pharmacokinetics {{pharma-stub