PHARMACOKINETIC DRUG-INTERACTIONS WITH GASTROINTESTINAL MOTILITY MODIFYING AGENTS

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 intestina l motility. These effects would be expected to increase the initial ra te of absorption of orally administered drugs, but reduce total bioava ilability of the agents. Metoclopramide has been shown to increase the rate of absorption of several classes of drug, reflected by reduced t ime taken to achieve maximal plasma concentration (t(max)) and increas ed maximal plasma concentration (C-max). However, the effect of these agents on the area under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)), when measured. is not consistent. Cisa pride and domperidone appear to have similar effects. but there are re latively less data available regarding these products. Opioids may del ay gastric emptying considerably, an effect which will often have sign ificant clinical and therapeutic implications, Most of the data confir ming this observation concern oral analgesics, but the effect should b e considered when prescribing any oral medication. Drugs with antichol inergic or sympathomimetic activity are likely to have a similar effec t and this is confirmed, in the main, by the limited data available. A lthough many effects reported in the literature are of limited clinica l importance, they may be significant when prescribing a drug with a n arrow therapeutic index. especially if it is absorbed poorly.