Kayhart Bryce, Lapid Maria I, Nelson Sarah, Cunningham Julie L, Thompson Virginia H, Leung Jonathan G
1 Hospital Pharmacy Services, Mayo Clinic Hospital, Rochester, MN, USA.
2 Mayo Clinic Department of Psychiatry and Psychology, Rochester, MN, USA.
Am J Hosp Palliat Care. 2018 Aug;35(8):1076-1080. doi: 10.1177/1049909117753828. Epub 2018 Jan 17.
In the absence of suitable oral or intravenous access for medication administration and when the intramuscular medications are undesirable, alternative routes for drug delivery may be considered. Antipsychotics administered via an inhaled, intranasal, rectal, or topical route have been described in the literature. Topically administered antipsychotics have been previously reported to produce negligible systemic absorption despite being used in clinical practice for nausea and behavioral symptoms associated with dementia. Additionally, the American Academy of Hospice and Palliative Medicine recommends against the use of topical medications that lack supporting literature. Three studies have assessed the systemic absorption of different antipsychotics after administration of only a single, topically applied dose. To evaluate whether the repeated administration of a topically applied antipsychotic may result in detectable serum levels in an accumulating fashion, a pharmacokinetic study was conducted. Five healthy, adult participants consented to receive extemporaneously prepared topical quetiapine in Lipoderm every 4 hours for a total of 5 doses. Blood samples were drawn at baseline and hours 2, 4, 8, 12, 16, and 24, and serum quetiapine concentrations were measured using high-performance liquid chromatography. Quetiapine was undetectable in every sample from 3 participants. Two participants had minimally detectable serum quetiapine levels no sooner than hour 12 of the study period. Extemporaneously prepared quetiapine in Lipoderm resulted in nonexistent or minimal serum level following repeated topical administration. The use of topically applied quetiapine should still be questioned.
在没有合适的口服或静脉给药途径且肌内用药不可取时，可以考虑其他给药途径。文献中已描述了通过吸入、鼻内、直肠或局部途径给药的抗精神病药物。尽管局部应用抗精神病药物在临床实践中用于治疗与痴呆相关的恶心和行为症状，但此前有报道称其全身吸收可忽略不计。此外，美国临终关怀与姑息医学学会建议不要使用缺乏文献支持的局部用药。有三项研究评估了仅单次局部应用不同抗精神病药物后的全身吸收情况。为了评估重复局部应用抗精神病药物是否可能以累积方式导致可检测到的血清水平，进行了一项药代动力学研究。五名健康成年参与者同意每4小时接受一次临时配制的含喹硫平的Lipoderm，共5剂。在基线以及第2、4、8、12、16和24小时采集血样，并使用高效液相色谱法测量血清喹硫平浓度。三名参与者的每个样本中均未检测到喹硫平。两名参与者在研究期第12小时后才出现最低可检测到的血清喹硫平水平。临时配制的含喹硫平的Lipoderm在重复局部给药后导致不存在或极低的血清水平。局部应用喹硫平的使用仍值得质疑。
