Department of Neuroscience, Neurology, Uppsala University, Sweden.
Acta Neurol Scand. 2013 Feb;127(2):124-32. doi: 10.1111/j.1600-0404.2012.01700.x. Epub 2012 Jul 4.
An oral dispersible microtablet formulation of levodopa/carbidopa 5/1.25 mg (LC-5) was developed for individualized repeated dosing. The aim was to compare pharmacokinetic profiles of LC-5 and levodopa/carbidopa/entacapone (LCE).
A randomized, crossover study was carried out in 11 healthy subjects. Plasma concentrations of levodopa, carbidopa and 3-O-methyldopa were determined after intake of 300 mg levodopa during the day, either as three intakes of 100/25/200 mg LCE or as a morning dose of 75/18.25 mg followed by five repeated doses of 45/11.25 mg LC-5.
Repeated dosing (2.4-hourly) with LC-5 microtablets compared to LCE (6-hourly) avoided long periods with low plasma levodopa levels. Time to maximum plasma concentrations was significantly shorter for LC-5. LC-5 showed lower fluctuation index (FI) in plasma compared to LCE (ANOVA P = 0.0028). FI for dose 2-5 was on average 1.26 for levodopa in LC-5, and 2.23 for dose 1-2 of LCE. The ratio between the two mean FI:s is 0.565; that is, LC-5 gave nearly half the FI as compared to LCE.
Fractionation of levodopa with LC-5 into small, frequent administrations as compared to standard administrations of LCE decreased the FI in plasma for both levodopa and carbidopa by nearly half.
开发左旋多巴/卡比多巴 5/1.25 毫克（LC-5）的口服分散片制剂，用于个体化重复给药。目的是比较 LC-5 和左旋多巴/卡比多巴/恩他卡朋（LCE）的药代动力学特征。
在 11 名健康受试者中进行了一项随机、交叉研究。在白天摄入 300 毫克左旋多巴后，分别以 LCE 的三种剂量（100/25/200 毫克）或 75/18.25 毫克的早晨剂量随后重复五次 45/11.25 毫克 LC-5 的方式，测定左旋多巴、卡比多巴和 3-O-甲氧基多巴的血浆浓度。
与 LCE（6 小时一次）相比，LC-5 微片剂的重复给药（每 2.4 小时一次）避免了长时间的低血浆左旋多巴水平。LC-5 的达峰时间显著缩短。LC-5 的血浆波动指数（FI）低于 LCE（方差分析 P = 0.0028）。LC-5 的第 2-5 剂的 FI 平均为左旋多巴的 1.26，而 LCE 的第 1-2 剂的 FI 为 2.23。这两个平均 FI 的比值为 0.565；也就是说，LC-5 与 LCE 相比，FI 降低了近一半。
与 LCE 的标准给药相比，LC-5 将左旋多巴分为小剂量、频繁给药，可使左旋多巴和卡比多巴的血浆 FI 降低近一半。
