Markowitz John S, Straughn Arthur B, Patrick Kennerly S, DeVane C Lindsay, Pestreich Linda, Lee James, Wang Yanfeng, Muniz Rafael
Department of Pharmaceutical Sciences, Medical University of South Carolina, Charleston, South Carolina 29425-0742, USA.
Clin Pharmacokinet. 2003;42(4):393-401. doi: 10.2165/00003088-200342040-00007.
To compare the rate and extent of absorption of DL-threo-methylphenidate (MPH) from two modified-release MPH formulations at their respective recommended starting doses in healthy adult volunteers.
Open-label, randomised, crossover, bioavailability study.
Twenty healthy adult male and female volunteers.
Subjects received single doses of two modified-release formulations of MPH, a 20mg capsule (Ritalin) LA) and an 18 mg tablet (Concerta). A total of 19 plasma samples was collected over 24 hours, and MPH plasma concentrations were determined by liquid chromatography-mass spectrometry (LC-MS/MS). These values were used to calculate standard noncompartmental pharmacokinetic parameters describing the rate (peak concentration and time to peak concentration) and extent (area under the concentration-time curve, AUC) of absorption of the two formulations. The relative bioavailability of the two drugs was assessed using a 90% confidence interval, based on the lower and upper endpoints of the confidence interval for the ratios of the geometric means (log transformed) being within the 0.80-1.25 equivalence criterion.
Nineteen subjects, ten male and nine female, aged 21-34 years completed both treatment phases of the study. The Ritalin LA formulation displayed a distinctly biphasic pharmacokinetic profile, with mean initial peak plasma concentration of 7 microg/L at an average of 2.1 hours after administration and a second peak of 9.3 microg/L occurring at 5.6 hours. In contrast, the profile of the Concerta formulation rapidly reached an initial plateau concentration of 3.4 microg/L at 3.3 hours after administration and a second mean plateau concentration of 5.9 microg/L approximately 6 hours after administration. Substantially more MPH was absorbed from Ritalin LA than from Concert over the first 4 hours; the respective AUC(4) values were 18.5 and 9.3 microg x h/L (p < 0.001). The overall extent of absorption of MPH was similar between the two formulations. Oral clearance was identical between the two dosage forms.
The Ritalin LA formulation exhibited more rapid initial absorption and reached significantly higher peak plasma concentrations compared with the Concerta formulation, although the oral bioavailability of MPH was similar between the two formulations. The Ritalin LA capsule demonstrated a distinctly bimodal plasma concentration-time profile. MPH plasma concentrations resulting from Concerta reached a peak at 6 hours. These results indicate that the recommended starting dose of the Ritalin LA 20 mg capsule formulation provides more rapid absorption and higher peak plasma concentrations than the recommended 18 mg starting dose of the Concerta formulation.
比较两种缓释哌醋甲酯（MPH）制剂在健康成年志愿者各自推荐起始剂量下的吸收速率和吸收程度。
开放标签、随机、交叉、生物利用度研究。
20名健康成年男性和女性志愿者。
受试者接受单剂量的两种MPH缓释制剂，一种20mg胶囊（利他林长效）和一种18mg片剂（康奈达）。在24小时内共采集19份血浆样本，通过液相色谱 - 质谱联用（LC - MS/MS）测定MPH血浆浓度。这些值用于计算描述两种制剂吸收速率（峰浓度和达峰时间）和吸收程度（浓度 - 时间曲线下面积，AUC）的标准非房室药代动力学参数。基于几何均值（对数转换）比值的置信区间下限和上限在0.80 - 1.25等效标准范围内，使用90%置信区间评估两种药物的相对生物利用度。
19名受试者（10名男性和9名女性，年龄21 - 34岁）完成了研究的两个治疗阶段。利他林长效制剂呈现明显的双相药代动力学特征，给药后平均2.1小时的初始血浆峰浓度为7μg/L，第二个峰浓度9.3μg/L出现在5.6小时。相比之下，康奈达制剂的曲线在给药后3.3小时迅速达到初始平台浓度3.4μg/L，给药后约6小时第二个平均平台浓度为5.9μg/L。在前4小时内，利他林长效制剂吸收的MPH显著多于康奈达制剂；各自的AUC(4)值分别为18.5和9.3μg·h/L（p < 0.001）。两种制剂中MPH的总体吸收程度相似。两种剂型的口服清除率相同。
与康奈达制剂相比，利他林长效制剂表现出更快的初始吸收，且达到显著更高的血浆峰浓度，尽管两种制剂中MPH的口服生物利用度相似。利他林长效胶囊呈现明显的双峰血浆浓度 - 时间曲线。康奈达产生的MPH血浆浓度在6小时达到峰值。这些结果表明，利他林长效20mg胶囊制剂的推荐起始剂量比康奈达制剂推荐的18mg起始剂量提供更快的吸收和更高的血浆峰浓度。
