of interactions. Buprenorphine conjugates with glucuronic acid, which explains the low bioavailability of only 5% in the case of oral administration. In the liver, buprenorphine is metabolised to norbuprenorphine (N-dealkylbuprenor- phine) and buprenorphine glucuronide. While the latter has no analgesic activity, norbuprenorphine exerts a weak analgesic action, but is of minor clinical importance (Ohtani et al 1995). After parenteral administration two thirds of the dose of buprenorphine is excreted unchanged in the faeces and one third is metabolised in the liver and eliminated as conjugates in the urine or bile (Heel et al 1979). In short-term treatment with buprenorphine, end-stage renal failure does not affect excretion of the drug. Side effects Buprenorphine has the typical side effects shown by all opioids including nausea, vomiting, dizziness, constipation, and headache. In a study of patients with chronic nociceptive pain, the analgesic efficacy of sublingual buprenorphine and sustained release morphine were similar, but the patients treated with buprenorphine had significantly fewer side effects (Bach et al 1991). This was particularly noticeable with respect to nausea, vomiting, and constipation and may in part be attributed to the sublingual route of administration bypassing the gut µ-opioid receptors. As with all other strong opioids, buprenorphine produces respiratory depression. In contrast with fentanyl and morphine, a ceiling effect has been shown to exist for buprenorphine-induced respiratory depression (Doxey et al 1982; Dahan et al 2005). This is consistent with the partial agonist profile of buprenorphine and the relevance of this factor with regard to the safety of the drug in clinical practice will be discussed later. The respiratory depressant effect of buprenorphine has been shown to respond to naloxone, an antagonist at the µ-opioid receptor, such that the effect can be completely reversed (Gal 1989; Dahan et al 2005). Clinical efficacy Buprenorphine is an effective analgesic with a potency at least 30 times that of morphine. The smallest dose recommended for IM use (0.3 mg) has been shown to be as effective as morphine (10 mg) but has a longer duration of action (6–18 hours) (Kay 1978). The accepted range for buprenorphine analgesic effects is 0.1–10 mg and in this range the drug behaves as an agonist with no flattening of the dose response curve at less than 100% effect. Buprenorphine given intravenously in the dose range of Therapeutics and Clinical Risk Management 2006:2(1) Safety of pain management with transdermal buprenorphine 0.4–7.0 mg for postoperative pain was found to be a potent, long-lasting safe analgesic with a minimum number of side effects, a dose-related efficacy and thus no ceiling effect for analgesia (Budd 1981). The treatment of neuropathic pain represents a challenge to clinicians and there is controversy regarding the efficacy of opioids in this condition. The abnormal pain sensitivity caused by neuropathy including hyperalgesia and allodynia is often resistant to opioid therapy. Buprenorphine has been shown to have a pronounced antihyperalgesic effect. In contrast to pure µ-agonists, buprenorphine-induced antihyperalgesic effects have a significant longer half life compared with its analgesic effects (Koppert et al 2005). These findings might account for the clinical efficacy in pain states dominated by hyperalgesia and central sensitization such as postoperative pain or neuropathic pain. Clinically, it has been shown that IV buprenorphine is effective in the treatment of post-thoracotomy neuropathic pain, albeit at a higher dosage than required to treat nociceptive postoperative pain (Benedetti et al 1998). Further, buprenorphine is the only opioid where antinociception is not blocked by pertussis toxin which is an experimental model to study the pathophysiology of neuropathic pain (Womer et al 1997; McCormack et al 1999). Sublingual buprenorphine tablets have undergone extensive evaluation as analgesic agents for acute and chronic cancer-related pain and have additionally become a valuable agent with which to treat opioid dependency. Transdermal delivery systems Transdermal delivery systems (TDS) have now been used for more than 10 years in situations other than pain management and have been shown to provide effective and well-tolerated drug delivery (Berner and John 1994; Ly et al 2001). They are not suited for all drugs but have several advantages over traditional routes of administration, including noninvasive administration and rate-controlled drug release. The TDS formulation is designed to overcome the pharmacokinetic problems of both oral and parenteral opioids including poor gastrointestinal absorption, first pass metabolism and low bioavailability. This formulation is particularly useful for patients with pre-existing gastro- intestinal problems and may improve patient compliance and quality of life. The high analgesic potency of buprenorphine, its high lipophilicity, and low molecular weight combined with a low abuse potential, make it an ideal drug for use in a TDS system. Together with another 117