Nyholm Dag, Lewander Tommy, Gomes-Trolin Cecilia, Bäckström Tobias, Panagiotidis Georgios, Ehrnebo Mats, Nyström Christer, Aquilonius Sten-Magnus
Department of Neuroscience, Neurology, Uppsala University, SE-75185 Uppsala, Sweden.
Clin Neuropharmacol. 2012 May-Jun;35(3):111-7. doi: 10.1097/WNF.0b013e31825645d1.
To compare bioavailability and pharmacokinetics of single doses of 3 different levodopa formulations given orally in healthy volunteers. Two marketed formulations, standard levodopa/carbidopa, 100/25 mg (LC-100), and dispersible levodopa/benserazide, 100/25 mg (LB-100), were used as reference formulations for a newly developed dispersible microtablet formulation of levodopa/carbidopa, 5/1.25 mg (LC-5). The microtablets are intended for individualized dosing of levodopa/carbidopa in Parkinson disease by means of an electronic dose dispenser with a built-in diary for symptom registration.
A single-dose, open, randomized, 3-way crossover study was performed in 19 healthy subjects. Concentrations of levodopa, carbidopa, and the metabolite 3-O-MD in plasma were determined after intake of 100 mg of levodopa, that is, one tablet of reference formulations and 20 microtablets of the new formulation.
The LC-5 microtablets were bioequivalent to the LC-100 tablets in area under the curve (AUC) and maximum concentration in plasma (Cmax) for levodopa, and to the LB-100 tablets in AUC. The dispersible levodopa/benserazide formulation showed earlier time to Cmax and significantly higher Cmax for levodopa in plasma compared to the microtablets. Carbidopa showed larger interindividual variation in AUC and Cmax than levodopa, and the bioequivalence comparison LC-5/LC-100 for this compound did not reach the target. Nevertheless, comparison of 3-O-MD levels for LC-5/LC-100, assuming proportionality to levodopa levels, demonstrated bioequivalence.
The new levodopa/carbidopa microtablets had a pharmacokinetic profile that would allow for a convenient switch of therapy from standard tablets. Frequent dose administration of levodopa/carbidopa microtablets with an electronic dose dispenser might offer an optimal oral drug delivery in Parkinson disease.
比较健康志愿者口服单剂量3种不同左旋多巴制剂的生物利用度和药代动力学。两种市售制剂，标准左旋多巴/卡比多巴100/25毫克（LC - 100）和可分散左旋多巴/苄丝肼100/25毫克（LB - 100），用作新开发的左旋多巴/卡比多巴5/1.25毫克可分散微片制剂（LC - 5）的参比制剂。这些微片旨在通过带有内置症状记录日记的电子剂量分配器，对帕金森病患者进行左旋多巴/卡比多巴的个体化给药。
在19名健康受试者中进行了一项单剂量、开放、随机、三交叉研究。在摄入100毫克左旋多巴后，即一片参比制剂和20片新制剂微片后，测定血浆中左旋多巴、卡比多巴和代谢物3 - O - MD的浓度。
LC - 5微片在左旋多巴的曲线下面积（AUC）和血浆最大浓度（Cmax）方面与LC - 100片生物等效，在AUC方面与LB - 100片生物等效。与微片相比，可分散左旋多巴/苄丝肼制剂的血浆左旋多巴Cmax出现时间更早且显著更高。卡比多巴在AUC和Cmax方面的个体间差异比左旋多巴更大，该化合物的生物等效性比较LC - 5/LC - 100未达到目标。然而，假设与左旋多巴水平成比例，LC - 5/LC - 100的3 - O - MD水平比较显示生物等效。
新的左旋多巴/卡比多巴微片具有的药代动力学特征使其能够方便地从标准片剂转换治疗。使用电子剂量分配器频繁给药左旋多巴/卡比多巴微片可能为帕金森病提供最佳的口服给药方式。
