CLINICAL-PHARMACOLOGY OF BUPRENORPHINE - CEILING EFFECTS AT HIGH-DOSES
CLINICAL-PHARMACOLOGY OF BUPRENORPHINE - CEILING EFFECTS AT HIGH-DOSES
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DOI：
10.1038/clpt.1994.71
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发表时间：
1994-05-01
影响因子：
6.7
通讯作者：
BIGELOW, GE
中科院分区：
文献类型：
--
作者：
WALSH, SL;PRESTON, KL;BIGELOW, GE
目的：本研究的目的是表征丁丙诺啡，阿片类药物的部分mu-激动剂，在广泛的剂量范围内的急性效应相比，美沙酮。方法：健康的成年男性志愿者，谁有经验，但身体上不依赖于阿片类药物，同时参加居住在一个封闭的研究单位。4例受试者接受丁丙诺啡（0、1、2、4、8、16和32 mg舌下给药），5例受试者接受美沙酮（0、15、30、45和60 mg口服给药），以递增顺序间隔1周。生理，主观和行为的措施进行了监测96小时后，药物administration.Results：这两种药物产生典型的阿片类激动剂的影响（积极的情绪，镇静，呼吸抑制，瞳孔缩小），其中一些持续24至48小时。观察到丁丙诺啡对主观测量和呼吸抑制的剂量效应达到平台期。药代动力学数据显示，丁丙诺啡的血浆浓度与剂量呈线性相关，表明在此剂量范围内舌下吸收没有限制：结论：这项研究表明，平台上丁丙诺啡的影响，符合其部分激动剂分类，和丁丙诺啡的单剂量高达70倍的推荐镇痛剂量耐受良好的非依赖人类。
Objective: The purpose of this study was to characterize the acute effects of buprenorphine, an opioid partial mu-agonist, across a wide range of doses in comparison to methadone.Method: Healthy adult male volunteers, who had experience with but were not physically dependent on opioids, participated while residing on a closed research unit. Four subjects received buprenorphine (0, 1, 2, 4, 8, 16, and 32 mg sublingually and five subjects received methadone (0, 15, 30, 45, and 60 mg orally) in ascending order at 1-week intervals. Physiologic, subjective, and behavioral measures were monitored for 96 hours after drug administration.Results: Both drugs produced typical opioid agonist effects (positive mood, sedation, respiratory depression, and miosis), some of which persisted for 24 to 48 hours. A plateau was observed for the dose effects of buprenorphine on subjective measures and respiratory depression. Pharmacokinetic data revealed that plasma concentrations of buprenorphine were linearly related to dose, indicating no limits on sublingual absorption in this dose range.Conclusions: This study shows a plateau on buprenorphine effects, consistent with its partial agonist classification, and that single doses of buprenorphine up to 70 times the recommended analgesic dose are well tolerated by nondependent humans.