Bioavailability and Analgesic Effect of Sustained Release Cetobemidone Capsules in Cancer Patients with Chronic Pain of Malignant Origin

Abstract

Ever since its introduction in 1952, Ketogan has consisted of a combination of the opioid cetobemidone and a spasmolytic drug, A29, in the ratio of 1:5. Its main limitations are the relatively short duration of action and an apparent ceiling effect due to A29. We therefore developed a cetobemidone formulation with sustained release properties (cetobem. s.r.). Forty-seven patients with advanced cancer with moderate/severe pain, treated with regular doses of Ketogan tablets took part in an open phase 1 type pharmacologic/toxicologic study comparing Ketogan tablets and cetobem. s.r. The patients spent at least 4 days in the department. After evaluation during 12 h with Ketogan tablets (3–4 dosing intervals), a loading phase lasting for 36 h with cetobem. s.r. given twice/24 h (total dose of Ketogan tablets per 24 h divided by 2), and synchronous reduction of the dose of Ketogan tablets, a similar evaluation period of 12 h was performed when on treatment with cetobem. s.r. alone. Comparison of data from the two observation periods showed the following: Average relative bioavailability 0.77 SD 0.28. Only 2 patients were remediated before 12 h when on cetobem. s.r. Duration of action mean 11.9 h, SD 0.3 h. There was no significant difference between Ketogan tablets and cetobem. s.r. periods concerning ‘time with no pain’. Side-effects were few. The only significant difference was dry mouth being more severe during the tablet period. Vital signs were unaffected by treatment. It is concluded that cetobem. s.r. can be given every 12 h to cancer patients with chronic pain with satisfactory analgesic effect, a very modest change in side-effect profile and no significant effects on vital signs when substituting cetobem. s.r. for Ketogan tablets in equal daily doses.