The effect of food intake on the pharmacokinetics of sustained-release morphine sulfate capsules.

The effect of food intake on the pharmacokinetics of sustained-release (SR) morphine sulfate capsules was assessed in 24 healthy male volunteers. Subjects were randomized to receive a single, 20-mg SR morphine sulfate capsule while fasting and immediately after consumption of a standard high-fat meal. Plasma samples were masked for pharmacokinetic analysis. Although the extent of absorption of the SR preparation was comparable in subjects in the fed and fasted states, plasma morphine concentrations were significantly lower at most sampling times up to 10 hours when the drug was administered after a high-fat meal. The rate of absorption of morphine from the SR capsule was slower with food intake as evidenced by a 13% decrease in the maximum concentration (Cmax), a 28% increase in the half-life of absorption, and a 19% increase in the time to Cmax. Results of this study indicate that food intake had an effect on the overall plasma-concentration-versus-time profile of the SR morphine sulfate oral preparation, the extent of which was not revealed by a comparison of Cmax and area under the plasma concentration-time curve values alone.