Pharmacokinetics and pharmacodynamics of twenty-four-hourly Kapanol compared to twelve-hourly MS Contin in the treatment of severe cancer pain

Pain. 1997 Feb;69(3):295-302. doi: 10.1016/S0304-3959(96)03269-1.


Twenty-four patients with severe pain related to cancer completed a randomised, double-blind, double-dummy, crossover study examining morphine pharmacokinetics and pharmacodynamics when the same 24-h morphine dose was administered using two modified release oral morphine formulations; either one dose of Kapanol (a new sustained release polymer coated pellet formulation administered in capsule form, Glaxo Wellcome group of companies) per 24 h, or MS Contin (Purdue Frederick Company, Connecticut, USA) administered at 12-h intervals. The morphine dose was optimised for each patient using an immediate release morphine solution in the lead-in period to provide the most favourable balance between pain relief and side-effects. Patients were then randomly allocated to receive their 24-h morphine dose as either Kapanol or MS Contin in period 1. Patients recorded daily measures of pain relief and morphine related side-effects (morphine pharmacodynamics) in a diary. Patients were admitted to the Pain Management Unit on the morning of day 7 (+/- 1 day) and frequent blood samples were collected for 24 h following the 10:00 h dose to fully characterise the pharmacokinetic profile for morphine and its metabolites at steady state. Morphine pharmacodynamics and the amount and timing of rescue medication (dextromoramide) were also recorded during this time. Period 2, which commenced at 10:00 h on day 8, was identical to period 1 except the modified release formulations were changed. The pharmacokinetic profile of Kapanol exhibited a significantly higher Cmin (minimum plasma morphine concentration), less fluctuation in plasma morphine concentration throughout the dosing interval, a longer Tmax (time associated with the maximum morphine concentration) and a greater time that the plasma morphine concentration was > or = 75% of Cmax (an index of the control the formulation exerts over the morphine release rate) compared to that of MS Contin. Some of these pharmacokinetic differences (e.g., Cmin and fluctuation in plasma morphine concentration) were surprising given that the dosing interval for Kapanol (24 h) was double that of MS Contin (12 h). There was no significant difference between the Kapanol and MS Contin treatment phases in any of the pharmacodynamic parameters, morphine related side-effects, the percentage of patients taking rescue medication as well as the amount or time to the first dose of rescue analgesia on day 7 in periods 1 and 2, patient or investigator assessments of global efficacy at the end of periods 1 and 2, or patient treatment preference at the end of the study. Once a day Kapanol provided the same degree of pain relief and morphine related side-effects as 12-h MS Contin.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analgesics, Opioid / pharmacokinetics
  • Analgesics, Opioid / therapeutic use*
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Morphine / pharmacokinetics
  • Morphine / therapeutic use*
  • Neoplasms / complications*
  • Neoplasms / metabolism
  • Pain / drug therapy*
  • Pain / etiology
  • Pain / metabolism
  • Treatment Outcome


  • Analgesics, Opioid
  • Delayed-Action Preparations
  • Morphine