复方卡比多巴和多巴丝肼的药代动力学和药效学比较研究

Comparative study on pharmacokinetics and pharmacodynamics of levodopa/carbidopa versus levodopa/benserazide

目的研究复方卡比多巴(左旋多巴/卡比多巴为250 mg/25 mg)和多巴丝肼(左旋多巴/苄丝肼为200 mg/50 mg)在帕金森病(PD)患者中的药代动力学及药效学特点。方法本试验用左旋多巴冲击实验,随机入组和交叉试验设计。20例PD患者第1周分别空腹口服复方卡比多巴275 mg或多巴丝肼250 mg,第2周接受另一种药物治疗。用高效液相色谱-串联质谱法检测左旋多巴血药浓度,用国际运动障碍协会帕金森病统一评分量表Ⅲ评估运动症状。结果有17例复方卡比多巴组和18例多巴丝肼组的患者数据纳入分析。服药后,复方卡比多巴组和多巴丝肼组的Cmax分别为(3563.76±1003.06)和(3642.44±1192.70)ng·mL^(-1),t_(max)分别为(1.10±0.44)和(1.03±0.55)h,t_(1/2)分别为(1.52±0.15)和(1.68±0.27)h,AUC_(0-t)分别为(7625.19±1706.85)和(5846.07±1191.16)ng·mL^(-1)·h,平均驻留时间(MRT)分别为(2.39±0.36)和(2.14±0.37)h。2组患者的C_(max)、t_(max)和t1/2比较,在统计学上差异均无统计学意义(均P>0.05);与多巴丝肼组相比,复方卡比多巴组中左旋多巴的AUC明显增加,MRT明显延长(均P<0.05)。2组各个时间点的运动症状改善和左旋多巴血药浓度呈现出较为一致的变化趋势,复方卡比多巴组在服药后第6和8小时的运动功能改善均显著优于多巴丝肼组[(-10.82±8.91)vs(-5.17±6.78)分,(-7.88±10.05)vs(-2.11±4.84)分;均P<0.05]。结论复方卡比多巴的药代动力学和药效学特点与多巴丝肼类似。

Objective To study the pharmacokinetic and pharmacodynamic characteristics of compound levodopa/carbidopa(250 mg/25 mg)and levodopa/benserazide(200 mg/50 mg)in patients with Parkinson’s disease(PD).Methods This experiment used a levodopa challenge test with a randomized crossover design.In the first week,20 PD patients orally received either 275 mg of compound levodopa/carbidopa or 250 mg of levodopa/benserazide on an empty stomach,and in the second week,they received the other treatment.The levodopa blood concentration was measured using high-performance liquid chromatography-tandem mass spectrometry,and motor symptoms were evaluated using the Movement Disorder Society-Unified Parkinson’s Disease Rating ScaleⅢ.Results Data from 17 patients in the compound levodopa/carbidopa group and 18 patients in the levodopa/ben se razide group was included in the analysis.After administration,the Cmax values of compound levodopa/carbidopa and levodopa/benserazide groups were(3563.76±1003.06)and(3642.44±1192.70)ng·mL^(-1);the t_(max) values were(1.10±0.44)and(1.03±0.55)h;the t1/2 values were(1.52±0.15)and(1.68±0.27)h;the AUC_(0-t) values were(7625.19±1706.85)and(5846.07±1191.16)ng·mL^(-1)·h;the mean residence time(MRT)values were(2.39±0.361)and(2.14±0.37)h,respectively.There were no statistically significant differences in the C_(max),t_(max),and t_(1/2) values between the two groups(all P>0.05).Compared with the levodopa/benserazide group,the compound levodopa/carbidopa group increased levodopa AUC and prolonged MRT(all P<0.05).The improvement in motor symptoms and levodopa blood concentration showed consistent trends at various time points in both groups.The compound levodopa/carbidopa group showed significantly better improvement in motor function at 6 and 8 hours after medication compared to the levodopa/benserazide group[(-10.82±8.91)points vs(-5.17±6.78)points,(-7.88±10.05)points vs(-2.11±4.84)points;both P<0.05].Conclusion The pharmacokinetic and pharmacodynamic characteristics of compound levodopa/carbidopa are similar to those of levodopa/benserazide.