Castrogiovanni P
Department of Neuroscience, Psychiatry Section, University of Siena, Siena, Italy.
Clin Ter. 2002 Mar-Apr;153(2):107-15.
The purpose of the study was to establish if the administration of a new slow-release formula of lithium carbonate (Carbothium Once-A-Day, 600 mg) administered once-daily could deliver plasma lithium levels during the first 24 hours similar to those obtained with two standard release Carbolithium 300 mg capsules administered 12 hours apart.
Eighteen healthy subjects of both sexes aged 18 to 55 were randomized to administration of either: [a] a single capsule of Carbolithium Once-A-Day (600 mg), or [b] standard Carbolithium 300 mg b.i.d. Subjects were crossed over following a 15-day washout period. Blood samples were taken 1, 2 4, 6, 8, 10, 12, 16, 20, 24, 36, 48, 72, and 96 hours post-drug administration and analyzed with spectrometry and atomic absorption to detect Li+ plasma concentration.
Data for individual subjects are reported as disjointed numerical values and as individual graphs in the paper. Mean AUC values were 3.01 mM-hours for standard Carbolithium vs. 3.53 mM-hrs for Carbolithium Once-A-Day, and respective mean levels across 96 hours were 0.214 +/- 0.107 vs. 0.252 +/- 0.097 mM. For the first 24 hours, mean AUC values were 2.64 for Carbolithium vs. 3.03 mM-hours for Carbolithium Once-A-Day, and corresponding means were 0.264 vs. 0.303 mM.
Carbolithium Once-A-Day was associated with marked reduction of the peak/trough ratio compared to standard release Carbolithium. Given the low therapeutic index of lithium, the maintenance of constant therapeutic concentrations under toxic limits is an essential characteristic of any clinically useful formulation. Furthermore, from the data obtained in the present study it is predicted that, for the majority of patients, a single dose of Carbolithium Once-A-Day will be sufficient to provide therapeutic concentrations of lithium for 24-hour periods. Even the few subjects who will require a double dosage with the Once-A-Day formulation will certainly experience less variations of Li+ plasma concentration throughout the day than would patients receiving rapid release formulations of lithium.
本研究的目的是确定每日服用一次的新型缓释碳酸锂配方（卡波锂一日一次，600毫克）在最初24小时内能否使血浆锂水平与每隔12小时服用两粒300毫克标准释放卡波锂胶囊所获得的水平相似。
18名年龄在18至55岁之间的健康男女受试者被随机分为两组，分别给予：[a]一粒卡波锂一日一次胶囊（600毫克），或[b]标准的卡波锂300毫克，每日两次。在15天的洗脱期后，受试者进行交叉试验。在给药后1、2、4、6、8、10、12、16、20、24、36、48、72和96小时采集血样，并用光谱法和原子吸收法分析以检测锂离子血浆浓度。
个体受试者的数据在论文中以离散数值和个体图表形式呈现。标准卡波锂的平均曲线下面积（AUC）值为3.01毫摩尔 - 小时，而卡波锂一日一次为3.53毫摩尔 - 小时，96小时内各自的平均水平分别为0.214±0.107与0.252±0.097毫摩尔。在最初24小时内，卡波锂的平均AUC值为2.64毫摩尔 - 小时，而卡波锂一日一次为3.03毫摩尔 - 小时，相应均值分别为0.264与0.303毫摩尔。
与标准释放的卡波锂相比，卡波锂一日一次的峰谷比显著降低。鉴于锂的治疗指数较低，在毒性限度内维持恒定的治疗浓度是任何临床有用制剂的基本特征。此外，从本研究获得的数据预测，对于大多数患者，单剂量的卡波锂一日一次足以在24小时内提供治疗浓度的锂。即使是少数需要使用一日一次制剂双倍剂量的受试者，其全天锂离子血浆浓度的变化肯定也会比接受锂速释制剂的患者少。
