Hydromorphone has been found to be safe and effective in patients with impaired renal or hepatic function, although it is advised to be used with caution and close monitoring owing to the increased exposure to (mean Cmax and AUC were 2- to 4-fold higher) and slower elimination of hydromorphone and its metabolites in these patients [25-29]. Glucuronidation is the main metabolic pathway of hydromorphone and the principal metabolite is hydromorphone-3-glucuronide.

It is unlikely that hydromorphone would be involved in drug interactions involving cytochrome P450 (CYP) because studies have shown hydromorphone is metabolised via non-CYP dependent pathways and Inhibitors,research,lifescience,medical only minimally metabolised by P450 enzymes [30,31]. Hydromorphone

also lacks the analgesically active metabolites of many opioids that may lead to respiratory depression if accumulated Inhibitors,research,lifescience,medical and demonstrates a very low plasma protein binding (< 30%) [32,33]. For these reasons OROS® hydromorphone may be especially suitable and predictable for elderly patients, patients with renal or hepatic insufficiency, and patients with multiple morbidities and medications. Two recent studies have compared Inhibitors,research,lifescience,medical OROS® hydromorphone to other commonly used opioid analgesics: CR morphine [34] and extended-release (ER) oxycodone [35]. In patients with cancer pain, clinical equivalence in terms of Brief Pain Inventory (BPI) scores for 'worst pain in the past 24 hours' was not demonstrated for OROS® hydromorphone and CR morphine. However, the negative

direction of the mean difference between the treatments was in favour of OROS® hydromorphone and comparable results were found for secondary efficacy measures Inhibitors,research,lifescience,medical such as assessments of pain interference with daily activities [34]. With OROS® hydromorphone, pain intensity scores were Inhibitors,research,lifescience,medical similar in the morning and evening (measured by BPI pain now AM and PM), and pain check details levels in the evening were significantly lower with OROS® hydromorphone compared with CR morphine. This confirms that OROS® hydromorphone provides consistent pain relief over 24 hours and that there is little end-of-dose failure pain. The half value duration (the time period in which the plasma level of the active either ingredient is over the half-maximum concentration) can be used to measure the prolongation of the duration of action of CR preparations and therefore test for end-of-dose failure pain; the half value duration of OROS® hydromorphone is between 27 and 29 hours [36]. In the second comparative study, once-daily OROS® hydromorphone and twice-daily ER oxycodone provided comparable levels of pain relief and reductions in pain severity, as well as improvements in investigator and patient global evaluation scores and subjective measures of daily function and sleep, in patients with chronic, moderate to severe osteoarthritis pain [35].