Efficacy, safety, and steady-state pharmacokinetics of once-a-day controlled-release morphine (MS Contin XL®) in cancer pain

The efficacy, safety, and pharmacokinetics of a novel once-daily morphine formulation (OAD morphine) and a 12-hourly formulation (twice-daily CR morphine) were compared in a double-blind, multi-centered crossover study. Chronic cancer pain patients (n = 25) were randomized to OAD morphine (mean 238 ± 319 mg q24h) or twice-daily CR morphine (mean 119 ± 159 mg q12h) for one week. They then crossed over to the alternate drug, which also was taken for one week. There was no difference between treatments for evaluations of overall pain intensity, analgesic efficacy, or adverse events. However, whereas pain scores increased during the day on twice-daily CR morphine (P = 0.0108), they remained stable on OAD morphine. Most patients (68%) chose once-daily dosing for continuing pain management (P = 0.015). The AUC ratio was 100.3%, indicating equivalent absorption. Fluctuation indices were 93.5 ± 28.8% and 179.3 ± 41.3% (P = 0.0001) for OAD morphine and twice-daily CR morphine, respectively. OAD morphine provides analgesia similar to twice-daily CR morphine with reduced fluctuation in plasma morphine concentration and more stable pain control.