Buprenorphine-induced acute respiratory depression during ifosfamide-based chemotherapy.

Buprenorphine is a potent, semi-synthetic opioid analgesic derived from thebaine. The drug displays the characteristics of an agonist at the mu receptors and antagonist at the kappa receptors. Although buprenorphine has shown some pharmacological effects on delta and kappa opioid receptors, the action on the mu receptors appears to be responsible for most of the analgesic effects associated with this compound. A new transdermal delivery system (TDS) has recently been introduced. This buprenorphine matrix patch is available in three doses, which releases 35, 52.5 and 70 lg/h, respectively; these rates correspond to daily doses of 0.8, 1.2 and 1.6 mg buprenorphine. Published data on the pharmacokinetic properties of buprenorphine administered by transdermal delivery system are limited [1]. A 34-year-old man with a partially resected osteosarcoma of the fronto-parietal skull and pelvic bone metastases entered our Oncology Unit. Ifosfamide 2 g/mq was administered once a day for 3 days as part of a sequential schedule also including doxorubicine, cisplatin and etoposide. In addition the patient received buprenorphine 35 lg/h to treat the pain. On admission he presented with proximal right limb somatic pain (VNS 7) due to his pelvic localisation. Physical examination and laboratory values were in the norm. Codeine 60 mg once a day and paracetamol 730 mg once a day was given without relief. On the first day of chemotherapy he started therapy with transdermal buprenorphine 35 lg/h/72. During the following 24 h he did not obtain any relief from pain so the buprenophine TDS dosage was increased to 52.5 lg/h. After 12 h he became confused and fell asleep easily. On medical examination he had a reduction of respiratory rate (from 20/min to 10/min), pupillary constriction and sinusal bradycardia (48 beats/min) on ECG. The transdermal buprenorphine was removed and vital parameters were monitored every 30 min. Over the following 12 h the patient had a slight and constant improvement, and after 24 h made a complete recovery. The efficacy of transdermal buprenorphine patches in treating chronic pain has been investigated in several multicentre randomised, double-blind placebo-controlled parallel group studies. Most of the enrolled patients had nonmalignant pain. Only in one trial [2] do we know how many patients were receiving concomitant chemotherapy. A high percentage of buprenorphine is bound to plasma protein and is metabolised in the liver by the cytochrome P450 3A4-enzyme system into norbuprenorphine and other products. Concomitant exposure to drugs that inhibit this enzyme may intensify the action of buprenorphine. Ifosfamide is a bifunctional alkylating agent, used as a racemic mixture by the intravenous route in the treatment of