在健康志愿者中，于不同饮食条件下对两种缓释哌甲酯制剂进行的药代动力学研究。

A pharmacokinetic study of two modified-release methylphenidate formulations under different food conditions in healthy volunteers.

作者信息

Haessler F, Tracik F, Dietrich H, Stammer H, Klatt J

机构信息

Clinic for Child Psychiatry, Neurology, Psychosomatics and Psychotherapy, University Hospital Rostock, Germany.

出版信息

Int J Clin Pharmacol Ther. 2008 Sep;46(9):466-76. doi: 10.5414/cpp46466.

DOI:10.5414/cpp46466

PMID:18793577

Abstract

OBJECTIVES

Primary objective was to investigate bioequivalence of Ritalin LA(R); 40 mg compared to Medikinet retard 40 mg in healthy male volunteers under fasted and fed conditions. Secondary objectives included assessment of tolerability and determination of further pharmacokinetic parameters. The difference between the kinetic profiles of Ritalin LA(R) and Medikinet retard with respect to breakfast intake was additionally explored.

METHODS

28 subjects were randomized in this open-label, four-treatment, cross-over-design study. Pharmacokinetic evaluations included AUC(0-inf), Cmax, tmax, elimination half life (t1/2) and mean residence time MRT(0-inf)). The relative bioavailability of Ritalin LA(R) and Medikinet retard and the food effect were assessed using a 90% confidence interval (CI) based on the lower and upper endpoints of the CI for the ratios of the geometric means being within the 80 - 125% equivalence criterion.

RESULTS

25 volunteers completed all treatment arms. Frequency of adverse events were comparable for all treatments. Under fasted condition Ritalin LA(R) showed a consistent bimodal concentration time profile with two tmax peaks. Medikinet retard showed a steady absorption with a single tmax peak. The point estimators for AUC(0-inf) and Cmax were found to be 99.7% and 85.9%, respectively. Under fed condition both Ritalin LA(R) and Medikinet retard showed a bimodal concentration time profile with two tmax peaks. The point estimators for AUC(0-inf) and Cmax were estimated as 89.8% and 68.6%, respectively.

CONCLUSIONS

Both methylphenidate formulations were safe and well tolerated. Ritalin LA and Medikinet retard were bioequivalent in fasted state but not in fed state. Only Ritalin LA had a biphasic kinetic profile under both fasted and fed conditions. This difference in the kinetic profiles might be of clinical relevance and might offer a potential advantage of Ritalin LA.

摘要

目的

主要目的是在健康男性志愿者的空腹和进食条件下，研究40毫克利他林长效制剂（Ritalin LA(R)）与40毫克美达莫缓释片（Medikinet retard）的生物等效性。次要目的包括耐受性评估和进一步药代动力学参数的测定。此外，还探讨了早餐摄入对利他林长效制剂和美达莫缓释片药代动力学曲线的差异。

方法

28名受试者被随机分配到这项开放标签、四治疗组、交叉设计的研究中。药代动力学评估包括药时曲线下面积（AUC(0-inf)）、最大血药浓度（Cmax）、达峰时间（tmax）、消除半衰期（t1/2）和平均驻留时间（MRT(0-inf)）。基于几何均值比的置信区间（CI）的下限和上限，使用90%置信区间评估利他林长效制剂和美达莫缓释片的相对生物利用度以及食物效应，几何均值比需在80 - 125%等效标准范围内。

结果

25名志愿者完成了所有治疗组。所有治疗的不良事件发生率相当。在空腹条件下，利他林长效制剂呈现出一致的双峰浓度 - 时间曲线，有两个达峰时间峰值。美达莫缓释片显示出稳定吸收，有一个单一的达峰时间峰值。发现AUC(0-inf)和Cmax的点估计值分别为99.7%和85.9%。在进食条件下，利他林长效制剂和美达莫缓释片均呈现双峰浓度 - 时间曲线，有两个达峰时间峰值。AUC(0-inf)和Cmax的点估计值分别估计为89.8%和68.6%。