Pharmacokinetic drug interactions with gastrointestinal motility modifying agents

Abstract

Drugs may affect gastrointestinal motility and, therefore, absorption of other concomitantly administered drugs. Gastrointestinal prokinetic agents increase the rate of gastric emptying and also upper intestinal motility. These effects would be expected to increase the initial rate of absorption of orally administered drugs, but reduce total bioavailability of the agents. Metoclopramide has been shown to increase the rate of absorption of several classes of drug, reflected by reduced time taken to achieve maximal plasma concentration (tmax) and increased maximal plasma concentration (Cmax). However, the effect of these agents on the area under the plasma concentration-time curve from zero to infinity (AUC0-infinity), when measured, is not consistent. Cisapride and domperidone appear to have similar effects, but there are relatively less data available regarding these products. Opioids may delay gastric emptying considerably, an effect which will often have significant clinical and therapeutic implications. Most of the data confirming this observation concern oral analgesics, but the effect should be considered when prescribing any oral medication. Drugs with anticholinergic or sympathomimetic activity are likely to have a similar effect and this is confirmed, in the main, by the limited data available. Although many effects reported in the literature are of limited clinical importance, they may be significant when prescribing a drug with a narrow therapeutic index, especially if it is absorbed poorly.