Steady-state kinetics and dynamics of morphine in cancer patients: is sedation related to the absorption rate of morphine?

摘要: Eighteen patients suffering from chronic pain due to cancer completed a balanced, double-blind, double-dummy, two period cross-over trial comparing the pharmacokinetics (PK) and pharmacodynamics (PD) of morphine its metabolites, morphine-3-glucuronide morphine-6-glucuronide, after administration given as controlled-release (CR) tablets (every 12 h) immediate-release (IR) 6 h). The same total daily dose was in both study periods. Patients received test formulations for 4 days on final day each period, peripheral venous blood samples analysis morphine, morphine-3-glucuronide, morphine-6-glucuronide were obtained. Pain intensity, sedation, continuous reaction time (CRT) assessed. No significant differences could be demonstrated AUC/dose, Cmin, Cmax or fluctuation index values between treatments (IR CR tablets) either metabolites. Tmax metabolites occurred significantly later than IR tablets. There no formulation with respect analgesia side effects, there difference patients' overall impression treatments. More important, peak sedation (P = 0.63). However, relatively small number variability data, statistical power only 0.074. risk type II error is 0.926. These data demonstrate PK PD similarities morphine. They suggest that may relationship (determined by absorption rate) but further evaluation this potential needed.