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肠道细菌对左旋多巴肠内凝胶输注疗法药代动力学的影响。

Impact of Intestinal Bacteria on Levodopa Pharmacokinetics in LCIG Therapy.

作者信息

Yamanishi Yuki, Choudhury Mohammed Emamussalehin, Yoshida Akira, Hosokawa Yuko, Miyaue Noriyuki, Tada Satoshi, Ando Rina, Murakami Shinobu, Miyamoto Hitoshi, Nagai Masahiro

机构信息

Department of Clinical Pharmacology and Therapeutics Ehime University Graduate School of Medicine Toon Japan.

Department of Molecular and Cellular Physiology Ehime University Graduate School of Medicine Toon Japan.

出版信息

Mov Disord Clin Pract. 2022 Feb 20;9(3):362-368. doi: 10.1002/mdc3.13417. eCollection 2022 Apr.

Abstract

BACKGROUND

Levodopa-carbidopa intestinal gel (LCIG) therapy is used in advanced Parkinson's disease (PD) and consists of continuous administration of levodopa directly into the jejunum through a percutaneous endoscopic gastro-jejunal (PEG-J) tube. Recently, the metabolism of levodopa by () has been reported. Intestinal bacteria can also affect this therapy.

OBJECTIVES

To investigate intestinal bacteria and examine its impact on levodopa blood concentration in patients with PD receiving LCIG therapy.

METHODS

We enrolled 6 patients receiving LCIG therapy in our department. After PEG-J tube replacement, intestinal bacteria were collected from the tip of the tube and were identified using culture and polymerase chain reaction (PCR) tests. Moreover, the presence of tyrosine decarboxylase, which metabolizes levodopa, was also confirmed by PCR test. The ability of these bacteria to metabolize levodopa was confirmed in vitro. Levodopa blood concentrations were also examined before PEG-J tube replacement.

RESULTS

Bacteria were detected in all 6 patients. was present in 4 patients. Moreover, tyrosine decarboxylase was detected in 2 patients. The identified bacteria displayed in vitro metabolization to dopamine in the 4 positive samples. The addition of carbidopa did not inhibit the metabolism of levodopa. However, there was no difference in the mean blood concentration of levodopa, regardless of the presence of .

CONCLUSIONS

We found bacteria, including in the PEG-J tube. We observed levodopa metabolism in vitro, but there was no association with levodopa blood concentration. The effect of intestinal bacteria may be limited in patients receiving LCIG therapy.

摘要

背景

左旋多巴-卡比多巴肠凝胶(LCIG)疗法用于晚期帕金森病(PD),通过经皮内镜胃空肠造瘘(PEG-J)管将左旋多巴持续输注至空肠。最近,有报道称左旋多巴可被(此处原文缺失相关内容)代谢。肠道细菌也可能影响这种治疗。

目的

研究接受LCIG治疗的PD患者的肠道细菌,并检测其对左旋多巴血药浓度的影响。

方法

我们纳入了6例在我科接受LCIG治疗的患者。在更换PEG-J管后,从管尖端采集肠道细菌,并通过培养和聚合酶链反应(PCR)检测进行鉴定。此外,还通过PCR检测确认了代谢左旋多巴的酪氨酸脱羧酶的存在。这些细菌代谢左旋多巴的能力在体外得到了证实。在更换PEG-J管前也检测了左旋多巴的血药浓度。

结果

6例患者均检测到细菌。4例患者中存在(此处原文缺失相关内容)。此外,2例患者检测到酪氨酸脱羧酶。在4例(此处原文缺失相关内容)阳性样本中,鉴定出的细菌在体外可将左旋多巴代谢为多巴胺。加入卡比多巴并未抑制左旋多巴的代谢。然而,无论是否存在(此处原文缺失相关内容),左旋多巴的平均血药浓度均无差异。

结论

我们在PEG-J管中发现了包括(此处原文缺失相关内容)在内的细菌。我们观察到了左旋多巴的体外代谢,但这与左旋多巴的血药浓度无关。在接受LCIG治疗的患者中,肠道细菌的影响可能有限。

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