morphine-6-glucuronide and Renal-Insufficiency--Chronic

Impairment of renal function is common among elderly patients due to an age-related decline in renal excretory function. In addition, many diseases such as hypertension and diabetes mellitus are associated with an accelerated decline in renal function. Renal dysfunction affects the metabolism of compounds and thus has important therapeutic consequences for drug safety. For pain patients who have reduced renal function such as those in palliative care, most opioids used for chronic pain treatment should be administered at reduced dosages, with increased dosage intervals, or not at all because of the risk of accumulation of the parent compound or its metabolites. For instance, for morphine or codeine, active metabolites are formed in the liver and cleared by the kidney and may therefore accumulate in cases of renal dysfunction. In contrast, buprenorphine can be administered at normal doses in patients with renal dysfunction because it is mainly excreted through the liver. In patients undergoing regular haemodialysis treatment, removal of an opioid during dialysis varies between individuals based upon a number of factors including the dialysis technique used. Morphine appears to be difficult to process in haemodialysis patients due to possible 'rebound' of metabolites between dialysis sessions. By contrast, the pharmacokinetics of buprenorphine are unchanged in haemodialysis patients, which means that there is no need for dose-reduction with this drug. Thus, in patients with reduced renal function, chronic renal insufficiency and haemodialysis, buprenorphine appears to be a safe choice when opioid treatment is initiated.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Analgesics, Opioid; Buprenorphine; Contraindications; Humans; Kidney; Kidney Function Tests; Middle Aged; Morphine; Morphine Derivatives; Pain; Renal Dialysis; Renal Insufficiency, Chronic

We prospectively investigated the efficacy of opioid rotation from oral morphine to oral oxycodone in cancer patients who had difficulty in continuing oral morphine treatment because of inadequate analgesia and/or intolerable side effects.. Twenty-seven patients were enrolled and 25 were evaluated. The rate of patients who achieved adequate pain control, which provided an indication of treatment success, was evaluated as primary endpoint. The acceptability and pharmacokinetics of oxycodone were evaluated in addition to the assessment of analgesic efficacy and safety during the study period.. In spite of intense pain, the morphine daily dose could not be increased in most patients before the study because of intolerable side effects. However, switching to oral oxycodone allowed approximately 1.7-fold increase as morphine equivalent dose. Consequently, 84.0% (21/25) of patients achieved adequate pain control. By the end of the study, all patients except one had tolerated the morphine-induced intolerable side effects (i.e. nausea, vomiting, constipation, drowsiness). Common side effects (>10%) that occurred during the study were typically known for strong opioid analgesics, and most were mild to moderate in severity. A significant negative correlation between creatinine clearance (CCr) value and the trough concentrations of the morphine metabolites was observed. On the other hand, no significant correlation was found between CCr value and the pharmacokinetic parameters of oxycodone or its metabolites.. For patients who had difficulty in continuing oral morphine treatment, regardless of renal function, opioid rotation to oral oxycodone may be an effective approach to alleviate intolerable side effects and pain.

Topics: Administration, Oral; Aged; Analgesics, Opioid; Constipation; Drug Administration Schedule; Female; Humans; Linear Models; Male; Middle Aged; Morphinans; Morphine; Morphine Derivatives; Nausea; Neoplasms; Oxycodone; Pain; Prospective Studies; Renal Insufficiency, Chronic; Sleep Stages; Treatment Outcome; Vomiting