Zulli C, Sica M, De Micco R, Del Prete A, Amato M R, Tessitore A, Ferraro F, Esposito P
Endoscopy Unit, Department of Clinical and Experimental Medicine "Magrassi e Lanzara", Second University of Naples, Naples, Italy.
Eur Rev Med Pharmacol Sci. 2016 Jun;20(11):2413-7.
Levodopa is the gold standard in the pharmacological treatment of Parkinson's disease (PD) and its oral administration is associated with the development of disabling motor and non-motor complications in advanced disease. Levodopa is rapidly metabolized and has a short plasma half-life thus requiring frequent, repeated dosing. Impaired gastric emptying is common in PD, and likely contributes to the unpredictable motor responses observed with orally-dosed levodopa. A new therapeutic protocol for patients with advanced PD include a carbidopa/levodopa combination using continuous, modulated enteral administration achieved inserting a Jejunal Extension Tube Placement through Percutaneous Endoscopic Gastrostomy (PEG-J). The aim of this work is to assess efficacy and safety of levodopa-carbidopa intestinal gel (LCIG) delivered continuously through an intrajejunal percutaneous tube (PEG-J).
We enrolled 11 adults with advanced PD and preserved sensitivity to L-dopa. For pre-procedural endoscopic evaluation each patient underwent a diagnostic esophagogastroduodenoscopy (EGD) 7 days before PEG-J placement to evaluate the presence of gastric anatomical or wall anomalies and the presence of oesophageal or gastric varices. Treatment with LCIG, consisting of a water-based suspension containing micronized levodopa (20 mg/mL) and carbidopa (5 mg/mL) in methylcellulose (Duodopa®), was administered by continuous jejunal infusion for 12h/day using a portable pump (CADD-Legacy) by PEG-J. Clinical evaluations were performed at baseline (T0) before LCIG initiation, and after 3 (T3) and 6 (T6) months of therapy. The efficacy and safety outcomes were assessed by using the Unified Parkinson's Disease Rating Scale (UPDRS) parts II, III and IV.
Mean age of patients was 71.18 ± 5.4 SD at LCIG initiation. Out of the 11 patients, 2 (18%) dropped-out LCIG at T3. Patients showed statistically significant (p < 0.05) higher performances in activities of daily living and a statistically significant (p < 0.001) lower incidence and severity of motor fluctuations, as rating by UPDRS part IV, compared to their best oral therapy. During observational period, 5 patients experienced adverse events. Success rate for PEG-J placement was 100%.
Our work shows that continuous intrajejunal infusion of LCIG ensures a reduction in motor Fluctuations compared to oral administration of levodopa-carbidopa in advanced PD. Based on our results and on the evidence emerging in the literature, this therapeutic approach should be the gold standard for therapy in these patients.
左旋多巴是帕金森病（PD）药物治疗的金标准，其口服给药与晚期疾病中致残性运动和非运动并发症的发生有关。左旋多巴代谢迅速，血浆半衰期短，因此需要频繁重复给药。PD患者胃排空受损很常见，这可能导致口服左旋多巴时出现不可预测的运动反应。一种针对晚期PD患者的新治疗方案包括使用卡比多巴/左旋多巴组合，通过经皮内镜下胃造口术（PEG-J）插入空肠延长管实现连续、调节性肠内给药。这项工作的目的是评估通过空肠内经皮管（PEG-J）持续输送左旋多巴-卡比多巴肠凝胶（LCIG）的疗效和安全性。
我们纳入了11名晚期PD且对左旋多巴仍保持敏感性的成年人。在进行PEG-J置入术前的内镜评估时，每位患者在PEG-J置入前7天接受诊断性食管胃十二指肠镜检查（EGD），以评估胃部解剖结构或壁异常情况以及食管或胃静脉曲张的存在情况。LCIG治疗由含微粉化左旋多巴（20mg/mL）和卡比多巴（5mg/mL）的甲基纤维素水基混悬液（Duodopa®）组成，通过PEG-J使用便携式泵（CADD-Legacy）进行空肠持续输注，每天12小时。在LCIG治疗开始前的基线（T0）以及治疗3个月（T3）和6个月（T6）后进行临床评估。使用统一帕金森病评定量表（UPDRS）第二、三、四部分评估疗效和安全性结果。
开始LCIG治疗时患者的平均年龄为71.18±5.4标准差。11名患者中，2名（18%）在T3时停用LCIG。与最佳口服治疗相比，患者在日常生活活动中的表现有统计学意义的提高（p<0.05），并且根据UPDRS第四部分评估，运动波动的发生率和严重程度有统计学意义的降低（p<0.001）。在观察期内，5名患者经历了不良事件。PEG-J置入的成功率为100%。
我们的研究表明，与晚期PD患者口服左旋多巴-卡比多巴相比，空肠内持续输注LCIG可确保减少运动波动。基于我们研究结果以及文献中出现的证据，这种治疗方法应成为这些患者治疗的金标准。
