Buprenorphine-induced acute respiratory depression during ifosfamide-based chemotherapy.
Buprenorphine-induced acute respiratory depression during ifosfamide-based chemotherapy.
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基于异环磷酰胺的化疗期间丁丙诺啡诱导的急性呼吸抑制。
DOI：
10.1093/annonc/mdl059
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
R. Labianca
中科院分区：
文献类型：
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作者：
C. Moro;R. Taino;M. Mandalà;R. Labianca
丁丙诺啡是一种强效的半合成阿片类镇痛药，来源于蒂巴因。该药物显示出μ受体激动剂和kappa受体拮抗剂的特征。尽管丁丙诺啡对δ和κ阿片受体显示出一些药理学作用，但对μ受体的作用似乎是与该化合物相关的大多数镇痛作用的原因。一种新的透皮给药系统（TDS）最近已被引入。这种丁丙诺啡基质贴剂有三种剂量，分别释放35、52.5和70 lg/h;这些速率对应于每日剂量0.8、1.2和1.6 mg丁丙诺啡。关于丁丙诺啡经皮给药系统给药的药代动力学特性的已发表数据有限[1]。一个34岁的男性，额顶骨骨肉瘤部分切除，骨盆骨转移进入我们的肿瘤科。异环磷酰胺2 g/mq每日一次给药，持续3天，作为序贯方案的一部分，还包括阿霉素、顺铂和依托泊苷。此外，患者接受丁丙诺啡35 lg/h治疗疼痛。入院时，由于骨盆定位，患者出现右侧肢体近端躯体疼痛（VNS 7）。体格检查和实验室检查值均正常。给予可待因60 mg每日一次和扑热息痛730 mg每日一次，未缓解。在化疗的第一天，他开始用经皮丁丙诺啡35 lg/h/72治疗。在接下来的24小时内，他没有获得任何疼痛缓解，因此丁丙诺啡TDS剂量增加至52.5 lg/h。12小时后，他变得困惑，很容易入睡。在医学检查中，他的呼吸频率降低（从20次/分降至10次/分），瞳孔收缩和窦性心动过缓（48次/分）。经皮丁丙诺啡被删除和生命参数进行监测，每30分钟。在接下来的12小时，病人有轻微的和不断的改善，并在24小时后完全恢复。已在多项多中心随机、双盲、安慰剂对照平行组研究中研究了丁丙诺啡透皮贴剂治疗慢性疼痛的疗效。大多数入组患者有非恶性疼痛。只有在一项试验[2]中，我们知道有多少患者接受了伴随化疗。高百分比的丁丙诺啡与血浆蛋白结合，并在肝脏中通过细胞色素P450 3A 4-酶系统代谢为降丁丙诺啡和其他产物。同时暴露于抑制这种酶的药物可能会加强丁丙诺啡的作用。异环磷酰胺是一种双功能烷化剂，作为外消旋混合物通过静脉途径用于治疗
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