Crevoisier C, Hoevels B, Zürcher G, Da Prada M
Clinical Research Department, Hoffmann-La Roche, Basle, Switzerland.
Eur Neurol. 1987;27 Suppl 1:36-46. doi: 10.1159/000116173.
Eight healthy male and fasted volunteers received alternatively either one HBS capsule of Madopar 125 or two HBS capsules of Madopar 125 or one standard capsule of Madopar 125 at weekly intervals with and without benserazide pretreatment (50 mg t.i.d. for 6 days). In this trial the Madopar formulations were administered 9.5 h after the last dose of benserazide. Serial blood samples were collected at various time intervals up to 12 h after Madopar dosing. Levodopa plasma concentrations were measured by high-performance liquid chromatography with electrochemical detection. After Madopar HBS without benserazide pretreatment the peak concentration (Cmax) of levodopa was lower and occurred at later times (tmax) than after standard Madopar. The mean values for tmax were 2.4, 2.8 and 0.8 h, whereas those for Cmax were 0.25, 0.56 and 1.38 micrograms/ml for one HBS capsule, two HBS capsules and standard Madopar, respectively. The mean relative bioavailability (versus standard Madopar) was 58 and 67% (value normalized to dose) for one and two HBS capsules, respectively. The parameter of half-value duration (= time span where plasma concentrations are equal to or higher than the half Cmax) was on average 3.5, 3.8 and 0.8 h for one HBS capsule, two HBS capsules and standard Madopar, respectively. Following benserazide pretreatment the mean tmax values for levodopa were 2.8, 2.3 and 0.8 h and the mean Cmax values were 0.35, 0.60 and 1.33 micrograms/ml, respectively, for one HBS capsule, two HBS capsules and standard Madopar. The relative bioavailability (versus standard Madopar) was 57 +/- 14 and 63 +/- 21% (value normalized to dose) for one and two HBS capsules, respectively. The mean values of the half-value duration were 3.6, 4.2 and 1.3 h for one HBS capsule, two HBS capsules and standard Madopar, respectively. For most of the parameters measured, the interindividual variability after Madopar HBS was less pronounced than after standard Madopar. In conclusion, according to these kinetic data, Madopar HBS shows the characteristics of a controlled-release formulation. The reduced bioavailability of the HBS form (60% of that of the standard form) suggests that a higher daily dose of Madopar HBS should be used for clinical practice.
八名健康男性空腹志愿者每隔一周交替服用一粒美多芭125的HBS胶囊、两粒美多芭125的HBS胶囊或一粒美多芭125标准胶囊，且分别在有和没有苄丝肼预处理（50mg，每日三次，共6天）的情况下进行。在该试验中，美多芭制剂在最后一剂苄丝肼给药9.5小时后服用。在美多芭给药后长达12小时的不同时间间隔采集系列血样。左旋多巴血浆浓度通过高效液相色谱电化学检测法测定。未进行苄丝肼预处理时，服用美多芭HBS后左旋多巴的峰值浓度（Cmax）较低且出现时间较晚（达峰时间tmax），低于服用标准美多芭之后。一粒HBS胶囊、两粒HBS胶囊和标准美多芭的tmax平均值分别为2.4、2.8和0.8小时，而Cmax平均值分别为0.25、0.56和1.38μg/ml。一粒和两粒HBS胶囊的平均相对生物利用度（相对于标准美多芭）分别为58%和67%（值经剂量归一化）。半衰期（即血浆浓度等于或高于Cmax一半的时间跨度）参数，一粒HBS胶囊、两粒HBS胶囊和标准美多芭的平均值分别为3.5、3.8和0.8小时。苄丝肼预处理后，一粒HBS胶囊、两粒HBS胶囊和标准美多芭的左旋多巴平均tmax值分别为2.8、2.3和0.8小时，平均Cmax值分别为0.35、0.60和1.33μg/ml。一粒和两粒HBS胶囊的相对生物利用度（相对于标准美多芭）分别为57±14%和63±21%（值经剂量归一化）。一粒HBS胶囊、两粒HBS胶囊和标准美多芭的半衰期平均值分别为3.6、4.2和1.3小时。对于所测量的大多数参数，美多芭HBS后的个体间变异性比标准美多芭后更不明显。总之，根据这些动力学数据，美多芭HBS显示出控释制剂的特征。HBS剂型生物利用度降低（为标准剂型的60%）表明，临床实践中应使用更高日剂量的美多芭HBS。
