Clinical efficacy, safety and pharmacokinetics of a newly developed controlled release morphine sulphate suppository in patients with cancer pain

Objective: To compare the efficacy, safety and pharmacokinetics of a newly developed controlled-release suppository (MSR) with MS Contin tablets (MSC) in cancer patients with pain. Methods: In a double-blind, randomised, two-way crossover trial, 25 patient s with cancer pain were selected with a morphine (M) demand of 30 mg every 12 h. Patients were divided into two groups. Group 1 received active MSC (3 0 mg) and placebo MSR, followed by placebo MSC and active MSR (30 mg) each for a period of 5 days. Group 2 started with active MSR and placebo MSG, fo llowed by active MSC and placebo MSR, each for a period of 5 days. Blood fo r determination of plasma concentration of morphine (M) and its 3- and 6-gl ucuronides (M3G, M6G) was collected, and area under the plasma concentratio n-time curve (AUC)(0-12) (h), peak plasma concentration (C-max), time to re ach C-max (t(max)), and C0 and C12 of M, M6G and M3G were determined on day 5 and day 10. Intensity of pain experienced by each patient was assessed e very 2 h on a 0-10 scale, while side effects and rescue medication were rec orded. Results: Twenty patients (ten patients in each group) completed the study. A pronounced inter-patient variability in plasma concentrations of M, M3G a nd M6G was observed after administration of both forms. Apart from the C0 a nd C12, no significant differences in AUC(0-12 h), t(max) and C-max of morp hine between the rectal and oral route of administration were found. In the case of the metabolites, it was found that AUC(0-12 h) and C-max of M6G, a nd AUC(0-12 h), C-max, C0 and C12 of M3G after rectal administration were s ignificantly lower than after oral administration. However, apart from the t(max) of M6G, none of the pharmacokinetic parameters of M, M6G or M3G met the criteria for bioequivalence. There were no significant (P = 0.44) diffe rences in pain intensity score between the oral and rectal forms within the two groups, regardless of the treatment sequence. No treatment differences in nausea, sedation or the demand on escape medication (acetaminophen tabl ets) between the rectal and oral forms were observed. Conclusion: The newly developed controled-release M suppository is safe and effective and may be a useful alternative for oral morphine administration in patients with cancer pain.