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注射用甜菜碱的制备及其在肺动脉高压中的治疗作用。

Preparation of betaine injection and its therapeutic effect in pulmonary arterial hypertension.

机构信息

Department of Pharmacology, College of Pharmacy, Ningxia Medical University, Yinchuan, Ningxia, China.

General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China.

出版信息

Basic Clin Pharmacol Toxicol. 2024 Feb;134(2):219-230. doi: 10.1111/bcpt.13966. Epub 2023 Dec 13.

Abstract

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterised by elevated pulmonary pressure, right ventricular failure (RVF) and ultimately death. Aggressive treatment of RVF is considered an important therapeutic strategy to treat PAH. Previous studies have indicated that betaine may be may a promising therapeutic approach for PAH-induced RVF. Therefore, in this study, betaine solution for injection was prepared and characterised using various techniques. The therapeutic efficacy of three different methods of administration (intragastric, nebulised inhalation and intravenous injection) were comprehensively evaluated in terms of pharmacokinetics, tissue distribution and pharmacodynamics. The pharmacokinetic results demonstrated that betaine injection administered via nebulised inhalation significantly prolonged betaine's half-life and increased its internal circulation time compared to the intragastric and intravenous routes. Biodistribution experiments verified that the betaine formulation accumulated in the lung tissue when administered via inhalation. The results of the pharmacodynamic analysis further confirmed that right ventricular systolic pressure, mean pulmonary artery pressure and right ventricular hypertrophy index increased in the model group and that inhaled betaine suppressed these pathological changes to a level comparable to those observed in the control group. Taken together, these results indicate that betaine administered by inhalation is a promising strategy for the treatment of PAH-induced RVF.

摘要

肺动脉高压(PAH)是一种危及生命的疾病,其特征是肺动脉压升高、右心室衰竭(RVF),最终导致死亡。积极治疗 RVF 被认为是治疗 PAH 的重要治疗策略。先前的研究表明,甜菜碱可能是治疗 PAH 诱导的 RVF 的一种很有前途的治疗方法。因此,在这项研究中,我们制备了注射用甜菜碱溶液,并使用各种技术对其进行了表征。从药代动力学、组织分布和药效学三个方面综合评价了三种不同给药途径(胃内、雾化吸入和静脉注射)的治疗效果。药代动力学结果表明,与胃内和静脉途径相比,雾化吸入给予的甜菜碱注射液显著延长了甜菜碱的半衰期并增加了其体内循环时间。生物分布实验证实,吸入给药时,甜菜碱制剂在肺组织中积累。药效学分析的结果进一步证实,模型组的右心室收缩压、平均肺动脉压和右心室肥厚指数增加,而吸入甜菜碱可抑制这些病理变化,使其达到与对照组相似的水平。综上所述,这些结果表明,吸入甜菜碱是治疗 PAH 诱导的 RVF 的一种有前途的策略。

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