Grahnén A, Eckernäs S A, Collin C, Ling-Andersson A, Tiger G, Nilsson M
Pharmaco Medical Consultants, PMC AB, Uppsala, Sweden.
Eur Neurol. 1992;32(6):343-8. doi: 10.1159/000116858.
The multiple-dose (200 mg levodopa t.i.d.) pharmacokinetic profile of two controlled-release products of levodopa (Madopar HBS and Sinemet CR) was compared to conventional Madopar capsules in 18 healthy volunteers in a cross-over, randomized design. A pronounced controlled-release profile of the Madopar HBS and Sinemet CR product was demonstrated compared to conventional Madopar capsules with a significant (p < 0.001) decrease (-40 and -55%) in Cmax and a significant (p < 0.001) increase (+237 and +256%) in morning Cmin for the 200 mg t.i.d. dosage schedule. Almost equivalent bioavailability (85-90%) of levodopa was demonstrated for the controlled-release formulations relative to that of conventional Madopar capsules. The Madopar HBS formulation was bioequivalent with Sinemet CR with respect to levodopa, but it exhibited a moderately higher fluctuation index compared to Sinemet CR as a result of somewhat higher Cmax and lower Cmin values for the Madopar HBS formulation. 3-OMD (a metabolite of levodopa) levels were significantly (p < 0.05) higher for Madopar HBS and Madopar compared to Sinemet CR. The higher 3-OMD levels for the levodopa/benserazide combinations are consistent with a more potent decarboxylase inhibitory activity of benserazide as compared to carbidopa. The number of adverse events was highest for conventional Madopar (n = 18) compared to the controlled-release formulations (n = 12 for Sinemet CR and only 2 for Madopar HBS). A more efficient inhibition of dopamine formation from levodopa (resulting in higher 3-OMD levels) by Madopar HBS was consistent with the superior tolerability (especially for initial nausea) observed for the Madopar HBS formulation as compared to Sinemet CR.
在一项交叉、随机设计中，对18名健康志愿者比较了两种左旋多巴控释制剂（美多芭HBS和息宁控释片）与传统美多芭胶囊的多剂量（左旋多巴200mg，每日三次）药代动力学特征。与传统美多芭胶囊相比，美多芭HBS和息宁控释片呈现出明显的控释特征，对于200mg每日三次的给药方案，Cmax显著降低（-40%和-55%，p<0.001），早晨Cmin显著升高（+237%和+256%，p<0.001）。相对于传统美多芭胶囊，控释制剂的左旋多巴生物利用度几乎相当（85-90%）。美多芭HBS制剂在左旋多巴方面与息宁控释片生物等效，但由于美多芭HBS制剂的Cmax略高和Cmin略低，其波动指数比息宁控释片略高。与息宁控释片相比，美多芭HBS和美多芭的3-OMD（左旋多巴的一种代谢物）水平显著更高（p<0.05）。左旋多巴/苄丝肼组合的3-OMD水平较高，这与苄丝肼相比卡比多巴具有更强的脱羧酶抑制活性是一致的。与控释制剂（息宁控释片n=12，美多芭HBS仅2例）相比，传统美多芭的不良事件数量最多（n=18）。美多芭HBS对左旋多巴形成多巴胺的抑制作用更强（导致3-OMD水平更高），这与美多芭HBS制剂相对于息宁控释片观察到的更好耐受性（尤其是对初始恶心）是一致的。
