Nutrient Effects on Intestinal Drug Absorption*

The effect of oral co-administration of nutrients on intestinal drug absorption is a function of drug dissolution, gastrointestinal (GI) residence time and intestinal membrane transport. Nutrient effects on GI residence time may influence the availability of the drug for absorption when dissolution is rate controlling; alternatively, nutrient effects on membrane transport pathways may dictate variability in drug absorption when these pathways are rate limiting. This report describes nutrient effects on the absorption variability of the anticonvulsant-antiarrhythmic drug, phenytoin (PHT). Numerous reports, detailing clinical failure to maintain drug plasma levels within the narrow therapeutic index of PHT, have implicated phenytoin-nutrient interactions as (possibly) causative. Absorption variability due to limited time for drug dissolution during GI transit was studied by measuring PHTplasma concentrations with time following oral dosage in dogs. Variability in intestinal uptake from PHT solutions as a function of nutrient inclusion was studied by measuring steady-state membrane permeabilities from intestinal perfusions and initial-rate uptakes by intestinal rings in rats.