Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Neurodegeneration In Vivo, Valby, Denmark.
J Pharm Pharmacol. 2017 Sep;69(9):1110-1115. doi: 10.1111/jphp.12758. Epub 2017 Jun 16.
Apomorphine is used to symptomatically treat Parkinson's disease (PD). Oral delivery of apomorphine is generally limited by its short plasma half-life and a hepatic first-pass metabolism. This study was aimed at evaluating the behavioural response of apomorphine and its prodrug administered in oral lipid-based formulations.
The behavioural response of apomorphine and its prodrug administered in oral lipid-based formulations was evaluated using a 6-hydroxydopamine-lesioned rat model simulating PD symptomatology. Apomorphine or dipalmitoyl apomorphine (DPA) was incorporated into different lipid-based formulations and orally administered (0.24 mmol/kg) to the PD rat model. The rotations by the rats were counted.
The duration of response lasted to about 2.5 h with oral apomorphine- and DPA-loaded o/w emulsion, while it was increased to 6 h when DPA was incorporated in self-emulsifying drug delivery systems compared to s.c. apomorphine (1 h). This suggests that the lipid-based formulations provide a sustained drug release allowing for a steady exposure to the brain.
Oral lipid-based apomorphine delivery has a potential in achieving a steady response, though at a higher dose possibly eliminating the need for frequent s.c. apomorphine administration.
阿扑吗啡用于治疗帕金森病（PD）的症状。口服阿扑吗啡通常受到其血浆半衰期短和肝脏首过代谢的限制。本研究旨在评估口服脂质体制剂中阿扑吗啡及其前药的行为反应。
使用模拟 PD 症状的 6-羟多巴胺损伤大鼠模型评估口服脂质体制剂中阿扑吗啡及其前药的行为反应。将阿扑吗啡或二棕榈酰阿扑吗啡（DPA）掺入不同的脂质体制剂中，并口服给予（0.24mmol/kg）PD 大鼠模型。计算大鼠的旋转次数。
口服阿扑吗啡和 DPA 负载的 o/w 乳剂的反应持续时间约为 2.5 小时，而当 DPA 被掺入自乳化药物递送系统时，与皮下阿扑吗啡（1 小时）相比，反应持续时间延长至 6 小时。这表明脂质体制剂提供了持续的药物释放，允许大脑稳定暴露于药物。
口服脂质体阿扑吗啡递送具有实现稳定反应的潜力，尽管需要更高的剂量，可能需要消除频繁的皮下阿扑吗啡给药。
