Effects of medicines used to treat gastrointestinal diseases on the pharmacokinetics of coadministered drugs: a PEARRL Review

Abstract

Objectives Drugs used to treat gastrointestinal diseases (GI drugs) are widely used either as prescription or over-the-counter (OTC) medications and belong to both the 10 most prescribed and 10 most sold OTC medications worldwide. The objective of this review article is to discuss the most frequent interactions between GI and other drugs, including identification of the mechanisms behind these interactions, where possible.Key findings Current clinical practice shows that in many cases, these drugs are administered concomitantly with other drug products. Due to their metabolic properties and mechanisms of action, the drugs used to treat gastrointestinal diseases can change the pharmacokinetics of some coadministered drugs. In certain cases, these interactions can lead to failure of treatment or to the occurrence of serious adverse events. The mechanism of interaction depends highly on drug properties and differs among therapeutic categories. Understanding these interactions is essential to providing recommendations for optimal drug therapy. Summary Interactions with GI drugs are numerous and can be highly significant clinically in some cases. While alterations in bioavailability due to changes in solubility, dissolution rate, GI transit and metabolic interactions can be (for the most part) easily identified, interactions that are mediated through other mechanisms, such as permeability or microbiota, are less well-understood. Future work should focus on characterising these aspects.

The Herb-Drug Pharmacokinetic Interaction of Fluoxetine and Its Metabolite Norfluoxetine with a Traditional Chinese Medicine in Rats by LC-MS/MS

“…As the dose of atropine increased, the area under the concentration-time curve (AUC) and the peak blood concentration of CyA decreased [25]. Drugs used to promote gastrointestinal motility can alter the pharmacokinetics of some coadministered drugs [26]. Fructus Aurantii flavonoids are one of the main components of Fructus Aurantii that possess prominent gastrointestinal motility promoting efficacy.…”

Clinical translation of advanced colonic drug delivery technologies

“…Moreover, GI disease can affect colonic physiology and function, and in turn affect drug behaviour and performance in patients [40][41][42][43][44]. For example, colonic pH is known to be reduced in IBD patients; changes to the epithelium and its transporters occur in colorectal cancer; and numerous diseases alter colonic transit time [9,45,46].…”

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“…An extensive review focusing on the alteration of GI transit time by laxatives was provided by Litou et al 87…”

“…An extensive review focusing on the alteration of GI transit time by laxatives was provided by Litou et al 87 Laxatives such as senna and bisacodyl have been reported to affect total and small intestinal transit times. Reduced GI transit time might affect the pharmacokinetics of coadministered drugs.…”