School of Pharmacy, University of Colorado Denver, 12631 E. 17th Ave., Mail Stop C238-L15, Aurora, CO 80045, USA.
Ann Pharmacother. 2009 Nov;43(11):1802-8. doi: 10.1345/aph.1M290. Epub 2009 Oct 13.
To summarize the published clinical data on fospropofol, critically review the safety and efficacy information, and provide pertinent information for formulary review.
Data were collected from searches of MEDLINE (1966-June 30, 2009), EMBASE (1974-June 30, 2009), bibliographies of manuscripts, and www.fda.gov. Key search terms included fospropofol, Lusedra, Aquavan, sedative-hypnotic, and monitored anesthesia care.
All Phase 1, Phase 2, and Phase 3 clinical trials studying the safety and efficacy of fospropofol were reviewed.
Fospropofol is a water-soluble prodrug of propofol, a potent sedative-hypnotic agent. Propofol is highly lipophilic and is formulated in lipid-containing solvents, which have known disadvantages, including pain on injection, narrow therapeutic window with the potential to cause deep sedation, high lipid intake during long-term sedation, and risk of infection resulting from bacterial contamination. Due to its water solubility, fospropofol eliminates some of the known lipid emulsion-associated disadvantages of propofol and provides a more predictable peak onset of activity and more gradual recovery to a full state of consciousness. The pharmacokinetic and pharmacodynamic profiles of fospropofol make it an attractive agent for sedation for procedures of short duration. Unfortunately, the number of patients studied has been relatively small and the amount of safety data is limited. Of concern are reports of hypoxemia and hypotension; these reports are limited in number, but the episodes are serious and may require acute intervention. Although fospropofol holds promise for procedural sedation, due to limited safety data, the Food and Drug Administration has limited approval of fospropofol to monitored anesthesia care in patients undergoing diagnostic or therapeutic procedures.
Fospropofol is a viable addition to the class of sedative-hypnotic agents due to the minimization of unwanted adverse effects of propofol and maintenance of a favorable pharmacokinetic profile facilitating sedation, anxiolysis, and rapid recovery. However, there are limited safety data to justify its use without the presence of dedicated anesthesia personnel.
总结已发表的关于磷丙泊酚的临床数据，严格审查安全性和疗效信息，为处方审核提供相关信息。
从 MEDLINE（1966 年-2009 年 6 月 30 日）、EMBASE（1974 年-2009 年 6 月 30 日）、手稿的参考文献和 www.fda.gov 中检索数据。主要检索词包括磷丙泊酚、Lusedra、Aquavan、镇静催眠药和监测麻醉护理。
所有研究磷丙泊酚安全性和疗效的 1 期、2 期和 3 期临床试验均被审查。
磷丙泊酚是丙泊酚的水溶性前体药物，丙泊酚是一种强效的镇静催眠药。丙泊酚具有很强的亲脂性，并且以含脂溶剂配制，这具有已知的缺点，包括注射疼痛、具有导致深度镇静的潜在窄治疗窗、长期镇静期间摄入大量脂肪以及由于细菌污染导致的感染风险。由于其水溶性，磷丙泊酚消除了丙泊酚中已知的一些脂乳剂相关缺点，并提供了更可预测的起效高峰和更缓慢的完全意识恢复。磷丙泊酚的药代动力学和药效学特征使其成为短时间手术镇静的有吸引力的药物。不幸的是，研究的患者数量相对较少，安全性数据有限。令人关注的是低氧血症和低血压的报告；这些报告数量有限，但发作严重，可能需要急性干预。尽管磷丙泊酚有望用于程序镇静，但由于安全性数据有限，食品和药物管理局仅批准磷丙泊酚在接受诊断或治疗程序的患者中用于监测麻醉护理。
由于丙泊酚的不良作用最小化，并保持有利的药代动力学特征，促进镇静、焦虑缓解和快速恢复，磷丙泊酚是镇静催眠药类的一个可行选择。然而，由于缺乏专用麻醉人员，安全性数据有限，无法证明其使用是合理的。
