Bioavailability of oxycodone by mouth in coronary artery bypass surgery patients - a randomized trial.

Antti Valtola, James D Morse, Pawel Florkiewicz, Heidi Hautajärvi, Pasi Lahtinen, Tadeusz Musialowicz, Brian J Anderson, Veli-Pekka Ranta, Hannu Kokki
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引用次数: 3

Abstract

Objective: Pain after coronary artery by-pass (CAB) surgery is severe. Analgesic administration by mouth is unreliable until after gastrointestinal function has recovered. We evaluated the bioavailability of oxycodone co-administered with naloxone by mouth in patients after CAB surgery using either a conventional extracorporeal circulation (CECC) or off-pump surgery (OPCAB).

Methods: Twenty-four patients, 50-73 years, 12 with CECC and 12 with OPCAB, were administered a 10/5 mg oxycodone-naloxone controlled-release tablet by mouth on the preoperative day and for the first seven postoperative days (PODs) thereafter. Blood samples were collected up to 24 h after the preoperative administration, and then randomly either on POD1 and POD3 or on POD2 and POD4. The oxycodone concentration in plasma was analyzed using liquid chromatography-mass spectrometry.

Results: On POD1 oxycodone absorption was markedly delayed in five of six patients after CECC and in all six patients after OPCAB surgery; median of tmax after CECC 630 [range 270-1420] minutes and after OPCAB 1020 [720-1410] minutes, compared to median of 120-315 min preoperatively and on POD2-POD4. The carry-over corrected AUC0-24 values on the PODs did not differ from the preoperative values, but were higher on POD3 compared with POD1 in both CECC and OPCAB groups. The rate and extent of oxycodone absorption equaled preoperative values on POD2 and onwards in patients with CAB surgery.

Conclusions: Bioavailability of oxycodone by mouth was similar after CAB surgery via CECC or having OPCAB. Data indicate that POD2 is an appropriate time to start oxycodone administration by mouth after CAB surgery.

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冠状动脉搭桥术患者口服羟考酮的生物利用度-一项随机试验。
目的:冠状动脉旁路移植术(CAB)术后疼痛严重。在胃肠功能恢复之前,口服镇痛是不可靠的。我们评估了口服羟考酮与纳洛酮联合给药的生物利用度,这些患者在CAB手术后使用常规体外循环(CECC)或非泵手术(OPCAB)。方法:24例患者,年龄50 ~ 73岁,其中CECC患者12例,OPCAB患者12例,术前1天及术后7天口服羟考酮-纳洛酮控释片10/ 5mg。术前给药后24 h采集血样,然后随机选择POD1和POD3组,或POD2和POD4组。采用液相色谱-质谱法分析血浆中氧可酮浓度。结果:6例CECC术后5例、OPCAB术后6例羟考酮在POD1上的吸收明显延迟;CECC术后tmax中位数为630[范围270-1420]分钟,OPCAB术后tmax中位数为1020[720-1410]分钟,而术前和POD2-POD4术后tmax中位数为120-315分钟。在CECC组和OPCAB组中,pod上的携带校正的AUC0-24值与术前值没有差异,但在POD3上高于POD1。在CAB手术患者中,氧可酮的吸收速率和程度与术前的POD2及以后的值相等。结论:经CECC行CAB术后口服羟考酮的生物利用度与经OPCAB术后相似。数据表明,POD2是CAB术后开始口服羟考酮的合适时间。
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Journal of Drug Assessment
Journal of Drug Assessment PHARMACOLOGY & PHARMACY-
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