Peak plasma concentrations after oral morphine: a systematic review

We performed a systematic review of 69 studies with information on 2146 subjects (454 patients and 1692 healthy volunteers) to examine the maximum plasma concentration (Cmax) and the time taken to reach maximum concentration (Tmax) for different oral morphine formulations, and to clarify factors contributing to variability. Data from healthy volunteers reflected that seen for patients but was less variable. There was minimal difference between single and multiple doses, suggesting no accumulation of morphine. For immediate-release morphine there was no difference in either dose-corrected Cmax or Tmax between solution and tablets, or between different salts. For controlled-release formulations, little difference was observed between brands. Only for once-daily formulations was there any difference in absorption between fed and fasted, with a Tmax for fed subjects considerably longer than for fasted. There was no evidence for any difference between values obtained by radioimmunoassay (RIA) or high-performance liquid chromatography (HPLC).