Guay David R P
Department of Experimental & Clinical Pharmacology, College of Pharmacy, University of Minnesota, MN 55455, USA.
Consult Pharm. 2007 May;22(5):417-30. doi: 10.4140/tcp.n.2007.417.
To review the pharmacodynamics, pharmacokinetics, efficacy, tolerability, dosing, and role of oral oxymorphone immediate-release (IR) and extended-release (ER).
A MEDLINE/PUBMED search (1970 to September 2006) of English language studies. Additional references were obtained from their bibliographies.
All human studies of oxymorphone were reviewed.
Oral oxymorphone IR/ER tablet formulations were approved in June 2006. Oxymorphone, a semi-synthetic -opioid receptor agonist structurally similar to hydromorphone, has an oral bioavailability of approximately 10%. Oxymorphone is extensively metabolized to oxymorphone-3-glucuronide and the active 6-hydroxyoxymorphone. Rapid clearance mandates every four- to six-hour dosing (IR) and every 12-hour dosing (ER). Hepatic impairment, renal impairment, and aging enhance systemic exposure. Oxymorphone IR was superior to placebo and oxycodone IR (acute pain studies). Oxymorphone ER was superior to placebo and equivalent to oxycodone CR and morphine CR (one acute and five chronic pain studies). Oxymorphone exhibits the expected opioid side effects, being comparable to oxycodone and morphine in clinical trials. Coadministration with ethanol causes "dose-dumping" (ER) and increases intersubject variability in drug absorption. Oxymorphone IR is indicated for the relief of moderate-to-severe pain, while oxymorphone ER is indicated for persistent pain. Initial doses (opioid-naïve) are 10 mg to 20 mg every 4 to 6 hours (IR) and 5 mg every 12 hours (ER). Dosage adjustment is recommended in mild hepatic impairment (Child-Pugh class A), renal impairment (creatinine clearance below 50 mL/min), and in the elderly.
Oxymorphone is the newest oral opioid to enter a crowded marketplace now totaling 12 Schedule 2 opioids. It does not appear to have any unique assets or liabilities and should be considered as one of many oral opioids for the management of acute and persistent pain of moderate-to-severe intensity.
综述口服即释型（IR）和缓释型（ER）羟吗啡酮的药效学、药代动力学、疗效、耐受性、给药剂量及作用。
检索MEDLINE/PUBMED（1970年至2006年9月）收录的英文研究。其他参考文献从其参考文献中获取。
对所有关于羟吗啡酮的人体研究进行综述。
口服羟吗啡酮IR/ER片剂剂型于2006年6月获批。羟吗啡酮是一种半合成的μ阿片受体激动剂，结构与氢吗啡酮相似，口服生物利用度约为10%。羟吗啡酮广泛代谢为羟吗啡酮-3-葡萄糖醛酸苷和活性代谢产物6-羟基羟吗啡酮。快速清除要求每4至6小时给药一次（IR），每12小时给药一次（ER）。肝功能损害、肾功能损害及老龄化会增加全身暴露量。羟吗啡酮IR在急性疼痛研究中优于安慰剂和羟考酮IR。羟吗啡酮ER在一项急性和五项慢性疼痛研究中优于安慰剂，且与羟考酮控释片和吗啡控释片相当。羟吗啡酮表现出预期的阿片类药物副作用，在临床试验中与羟考酮和吗啡相当。与乙醇合用会导致“剂量倾泻”（ER），并增加受试者间药物吸收的变异性。羟吗啡酮IR适用于缓解中重度疼痛，而羟吗啡酮ER适用于持续性疼痛。初始剂量（未使用过阿片类药物者）为每4至6小时10毫克至20毫克（IR），每12小时5毫克（ER）。建议在轻度肝功能损害（Child-Pugh A级）、肾功能损害（肌酐清除率低于50 mL/分钟）及老年人中调整剂量。
羟吗啡酮是进入竞争激烈的市场的最新口服阿片类药物，目前该市场共有12种附表2阿片类药物。它似乎没有任何独特的优势或劣势，应被视为用于治疗中重度急性和持续性疼痛的众多口服阿片类药物之一。
