Analgesic Effect and Bioavailability of Oral Ketogan Given as Tablets or Mixture to Patients with Chronic Pain of Malignant Origin

Abstract

Thirteen cancer patients with moderate to severe chronic pain of malignant origin on treatment with Ketogan tablets were included in an open non-randomized cross-over study comparing the analgesic effect, side effects and serum concentrations of Ketogan tablets and mixture. The patients were six days in hospital and were dosed two days with tablets, two days with mixture and finally another two days with tablets. Recordings of pain and side effects and collection of blood samples prior to dosing and hourly thereafter until remedication were performed on the second day of each dosing period in a morning dose interval. The analgesic effect judged by visual analog score (VAS) and pain intensity differences (PID), the areas under the serum concentration time curves, and the average serum concentrations for the three groups were compared. It was not possible do detect any differences among the three groups concerning the analgesic effect, duration of analgesic effect, the serum concentrations and the side effects. The mean plasma half-life of ketobemidone was 2.74 h ± 0.90 (SD) and the mean relative bioavailability of the mixture was slightly above 100%. Linear regression analysis revealed a significant correlation between ketobemidone serum concentrations and analgesic effect, VAS, for tablet one and for the mixture but not for tablet two, possibly due to the fixed dosing schedule and to the positive effect of hospitalization on the pain.