RANDOMIZED CROSSOVER COMPARISON OF THE PHARMACOKINETIC PROFILES OF 2 SUSTAINED-RELEASE MORPHINE-SULFATE FORMULATIONS IN PATIENTS WITH CANCER-RELATED PAIN

While morphine is an effective and well tolerated analgesic drug for m oderate or severe cancer-related pain, the utility of liquid formulati ons of this agent can be limited by poor compliance because of the nee d for frequent administration. Compliance can be improved with the use of sustained release (SR) oral formulations, which can achieve good t herapeutic efficacy with administration twice a day. The aim of this s tudy was to compare the bioequivalence of 2 SR formulations of morphin e 60mg: M-Eslon((R)) (capsules containing SR morphine sulfate microgra nules) and MS Contin((R)) (tablets). The study included 12 patients (7 males, 5 females) aged 37 to 75 (mean 57) years requiring strong opia tes for cancer-related pain, according to World Health Organization cr iteria. All patients had stable malignant disease and a Karnofsky perf ormance status >50. After a 7-day stabilisation period during which al l patients received morphine solution 120 mg/day, patients were random ised 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 b etween 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 c oncentrations of morphine. No significant between-group differences we re apparent for all pharmacokinetic parameters assessed on days 1 and 6 (Schuirmann's test). Opiate-related adverse events were observed wit h about the same frequency in both groups. The results of this study s uggest 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.