Controlled release morphine sulphate tablets‐‐a study in normal volunteers.

Indomethacin 25 mg four times daily and tromaril 600mg three times daily are therapeutically used doses comparable in terms of anti-inflammatory and PG-synthetase inhibitor activity. The treatment was not randomized because duration of PG synthetase inhibitor activity for tromaril is not known. There is therefore uncertainty regarding duration of washout period that would be necessary after tromaril. All the volunteers received indomethacin first, then tromaril. Urine was collected 6 hourly, and electrolytes estimated using flame photometry. The duration of PG-synthetase inhibitor activity of 50 mg indomethacin three times daily has been shown to be 30 h (Rane, Oelz, Frolich, Seyberth, Sweetman, Watson, Wilkinson & Oates, 1978). A washout period of 60 h was therefore given after indomethacin. There was no statistically significant difference between urine output and electrolyte excretion on control day prior to tromaril and indomethacin thus showing that the washout period after indomethacin was adequate. Indomethacin decreased sodium and chloride excretion in 0-12 h period. However, probably due to homeostatic mechanisms the 24 h output was unaltered.