[息宁与葛雷克（左旋多巴/卡比多巴250/25毫克）在帕金森病中的药代动力学比较：单剂量研究]

[Pharmacokinetic comparison of Sinemet and Grifoparkin (levodopa/carbidopa 250/25 mg) in Parkinson s disease: a single dose study].

作者信息

Chaná Pedro, Fierro Angélica, Reyes-Parada Miguel, Sáez-Briones Patricio

机构信息

Unidad de Movimientos Anormales, Servicio de Neurología y Neurocirugía, Hospital DIPRECA.

出版信息

Rev Med Chil. 2003 Jun;131(6):623-31.

PMID:12942590

Abstract

BACKGROUND

There are doubts wether generic medications have the same bioavailability and efficacy compared with the original drugs developed by pharmaceutical companies with research capabilities.

AIM

To compare the pharmacokinetics and clinical (motor) responses of Sinemet and Grifoparkin (generic carbidopa/levodopa 250/25 mg) in patients with advanced Parkinson's disease.

PATIENTS AND METHODS

Patients were randomly assigned to Sinemet (15 patients 62 +/- 12 years old; mean disease duration 11 +/- 7 years) or Grifoparkin (15 patients, 64 +/- 11 years old; mean disease duration 12 +/- 4 years) groups. Medication and food were withheld 12 h before the study. Fifteen blood samples were collected (starting 9 AM) immediately before (sample 1, t = 0 min) and after (samples 2-15, t = 20-360 min) oral administration of a single dose of Sinemet or Grifoparkin, and plasmatic L-DOPA was quantified using HPLC with electrochemical detection. Additionally, each patient was clinically evaluated every 20 minutes, using the tapping test and the unified Parkinson's disease scale Hoehn & Yarh.

RESULTS

Tmax (time at which the maximal L-DOPA concentration was reached) were 69 +/- 12 min and 64 +/- 11 min for Sinemet and Grifoparkin respectively (NS). Cmax (maximal L-DOPA concentration reached) was 3161 +/- 345 ng/ml for Sinemet and 3274 +/- 520 ng/ml for Grifoparkin (NS). The t1/2 (half life time), CL (clearance) and volume of distribution (Vd) values calculated were 159 +/- 32 min, 51.7 +/- 5.1 1/h and 3.6 +/- 1.2 l/kg for Sinemet and 161 +/- 48 min, 58.7 +/- 8 l/h and 3.0 +/- 0.7 l/kg for Grifoparkin (NS). UPDRS-III value for the best "on state" and for the worst "off state" were 23 +/- 11 and 50 +/- 19 for Sinemet and 20 +/- 7 and 46 +/- 13 for Grifoparkin respectively (NS).

CONCLUSION

The results obtained showed that both drugs are bioequivalent in patients with advanced Parkinson's disease.

摘要

背景

对于仿制药与具备研发能力的制药公司所研发的原研药相比，是否具有相同的生物利用度和疗效存在疑问。

目的

比较息宁和葛立复（通用名卡比多巴/左旋多巴250/25毫克）在晚期帕金森病患者中的药代动力学和临床（运动）反应。

患者和方法

患者被随机分配到息宁组（15例患者，年龄62±12岁；平均病程11±7年）或葛立复组（15例患者，年龄64±11岁；平均病程12±4年）。在研究前12小时停用药物和食物。在口服单剂量息宁或葛立复之前（样本1，t = 0分钟）和之后（样本2 - 15，t = 20 - 360分钟）立即采集15份血样（从上午9点开始），并使用带有电化学检测的高效液相色谱法定量血浆左旋多巴。此外，每隔20分钟对每位患者进行临床评估，采用敲击试验和统一帕金森病评定量表 Hoehn & Yarh。

结果

息宁和葛立复的达峰时间（达到最大左旋多巴浓度的时间）分别为69±12分钟和64±11分钟（无统计学差异）。息宁的峰浓度（达到的最大左旋多巴浓度）为3161±345纳克/毫升，葛立复为3274±520纳克/毫升（无统计学差异）。计算得到的息宁的半衰期（t1/2）、清除率（CL）和分布容积（Vd）值分别为159±32分钟、51.7±5.1升/小时和3.6±1.2升/千克，葛立复分别为161±48分钟、58.7±8升/小时和3.0±0.7升/千克（无统计学差异）。息宁在最佳“开期”和最差“关期”的UPDRS - III值分别为23±11和50±19，葛立复分别为20±7和46±13（无统计学差异）。