Randomised crossover comparison of the pharmacokinetic profiles of two sustained release morphine sulfate formulations in patients with cancer-related pain

While morphine is an effective and well tolerated analgesic drug for moderate or severe cancer-related pain, the utility of liquid formulations of this agent can be limited by poor compliance because of the need for frequent administration. Compliance can be improved with the use of sustained release (SR) oral formulations, which can achieve good therapeutic efficacy with administration twice a day. The aim of this study was to compare the bioequivalence of 2 SR formulations of morphine 60mg: M-Eslon((R)) (capsules containing SR morphine sulfate microgranules) and MS Contin((R)) (tablets). The study included 12 patients (7 males, 5 females) aged 37 to 75 (mean 57) years requiring strong opiates for cancer-related pain, according to World Health Organization criteria. All patients had stable malignant disease and a Karnofsky performance status >50. After a 7-day stabilisation period during which all patients received morphine solution 120 mg/day, patients were randomised to receive SR morphine 60mg capsules or tablets twice a day for 6 days according to a crossover design. During a 2-day washout period between treatments, analgesia was maintained with morphine syrup 120 mg/day. Venous blood samples were taken at 0, 15, 30, 60, 120, 240, 480 and 720 minutes after the morning doses on days 1 and 6 of treatment, and high performance liquid chromatography was used to assess plasma concentrations of morphine. No significant between-group differences were apparent for all pharmacokinetic parameters assessed on days 1 and 6 (Schuirmann's test). Opiate-related adverse events were observed with about the same frequency in both groups. The results of this study suggest that the pharmacokinetic profiles of the two formulations of SR morphine are equivalent after single and repeated oral administration in patients with cancer-related pain.