新配制的左旋多巴和卡比多巴多颗粒基质的药理学和药代动力学评价。

IF 3.4 Q2 CHEMISTRY, MEDICINAL ADMET and DMPK Pub Date : 2023-01-01 DOI:10.5599/admet.1474
Emelia Priscilla Imbeah, Ofosua Adi-Dako, Benoit Banga N'guessan, Kennedy Kwami Edem Kukuia, Benedicta Obenewaa Dankyi, Ismaila Adams, Ebenezer Ofori-Attah, Regina Appiah-Opong, Seth Kwabena Amponsah
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引用次数: 0

摘要

在帕金森病的治疗中,左旋多巴通常与卡比多巴联合使用。虽然上述联合治疗是有效的,但口服左旋多巴后血浆水平可能会出现波动。我们制定并评价了壳聚糖-果胶为基础的左旋多巴和卡比多巴多颗粒基质的动力学特性。从可可壳中提取果胶,采用湿法制备壳聚糖-果胶基基质。评价制剂与赋形剂的相容性、药物含量、预压缩性能和体外释放度。采用壳聚糖-果胶基左旋多巴/卡比多巴基质、Sinemet®CR或左旋多巴/卡比多巴速释粉剂对大鼠进行药动学评价。大鼠每12小时给予不同配方的左旋多巴/卡比多巴(20/5 mg/kg)。测定各治疗组左旋多巴的药动学参数。各制剂中左旋多巴和卡比多巴的含量均在验收标准范围内。左旋多巴/卡比多巴多颗粒基质(剂型3:484.98±18.70 μg.hr/mL)的AUC0-24;制剂4:535.60±33.04 μg.hr/mL), Cmax(制剂3:36.28±1.52 μg/mL;配方4:34.80±2.19 μg/mL)高于Sinemet®CR (AUC0-24 262.84±16.73 μg。Cmax为30.62±3.37 μg/mL)。与Sinemet®CR相比,新配方的t1 /2更长。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Pharmaceutical and pharmacokinetic evaluation of a newly formulated multiparticulate matrix of levodopa and carbidopa.

Levodopa is routinely co-administered with carbidopa in the management of Parkinson's disease. Although the aforementioned combination therapy is effective, there may be fluctuating plasma levels of levodopa after oral administration. We formulated and evaluated the kinetic characteristics of the chitosan-pectin-based multiparticulate matrix of levodopa and carbidopa. Pectin was extracted from the cocoa husk, and the chitosan-pectin-based matrix was prepared by wet granulation. Formulations were evaluated for drug-excipient compatibility, drug content, precompression properties and in vitro release. For pharmacokinetic evaluation, rats were put into groups and administered either chitosan-pectin based matrix of levodopa/carbidopa, Sinemet® CR or levodopa/carbidopa immediate release powder. Rats were administered the different formulations of levodopa/carbidopa (20/5 mg/kg) per os every 12 hours. The pharmacokinetic parameters of levodopa were estimated for the various treatment groups. The percentage content of levodopa and carbidopa in the various formulations was within the acceptance criteria. The AUC0-24 for levodopa/carbidopa multiparticulate matrix (Formulation 3: 484.98 ± 18.70 μg.hr/mL); Formulation 4: 535.60 ± 33.04 μg.hr/mL), and Cmax (Formulation 3: 36.28 ± 1.52 μg/mL; Formulation 4: 34.80 ± 2.19 μg/mL) were higher than Sinemet® CR (AUC0-24 262.84 ± 16.73 μg.hr/mL and Cmax 30.62 ± 3.37 μg/mL). The t 1/2 of the new formulation was longer compared to Sinemet® CR.

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来源期刊
ADMET and DMPK
ADMET and DMPK Multiple-
CiteScore
4.40
自引率
0.00%
发文量
22
审稿时长
4 weeks
期刊介绍: ADMET and DMPK is an open access journal devoted to the rapid dissemination of new and original scientific results in all areas of absorption, distribution, metabolism, excretion, toxicology and pharmacokinetics of drugs. ADMET and DMPK publishes the following types of contributions: - Original research papers - Feature articles - Review articles - Short communications and Notes - Letters to Editors - Book reviews The scope of the Journal involves, but is not limited to, the following areas: - physico-chemical properties of drugs and methods of their determination - drug permeabilities - drug absorption - drug-drug, drug-protein, drug-membrane and drug-DNA interactions - chemical stability and degradations of drugs - instrumental methods in ADMET - drug metablic processes - routes of administration and excretion of drug - pharmacokinetic/pharmacodynamic study - quantitative structure activity/property relationship - ADME/PK modelling - Toxicology screening - Transporter identification and study
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