Modi N B, Wang B, Hu W T, Gupta S K
Department of Clinical Pharmacology, ALZA Corp, 1900 Charleston Road, Mountain View, CA 94039, USA.
Biopharm Drug Dispos. 2000 Jan;21(1):23-31. doi: 10.1002/1099-081x(200001)21:1<23::aid-bdd212>3.0.co;2-v.
The effect of a high-fat meal on the pharmacokinetics of OROS(R) (methylphenidate HCl), an osmotic controlled-release formulation of methylphenidate HCl, was investigated in healthy subjects. Mean peak methylphenidate plasma concentrations occurred slightly later and peak methylphenidate plasma concentrations and AUC values were slightly higher (approximately 10-30%) in the presence of food than in the absence of food. There was no difference in the plasma elimination half-life of methylphenidate between the fed and fasted state. Similarly, peak concentrations and AUC values for alpha-phenyl-2-piperidine acetic acid (PPA; ritalinic acid), the major metabolite of methylphenidate, were slightly higher in the presence of food than in its absence. The 90% confidence interval (CI) for the treatment ratio (fed/fasted) for C(max) was 120.6%-140. 0% for the 18-mg dose and 105.4-119.3% for a 36-mg dose. The 90% CI for the treatment ratio for AUC(infinity) was 114.6-125.7% for the 18-mg dose and 115.1-124.6% for the 36-mg dose. PPA levels were measured following the 18-mg dose and the 90% CI of the treatment ratio was 106.8-115.4% for C(max) and 97.9-103.6% for AUC(infinity). These results indicate the absence of dose dumping from OROS (methylphenidate HCl) in the presence of food. Food does not impede drug absorption and OROS (methylphenidate HCl) may be administered in the fed or fasted state. There were no differences in the adverse event profile between the fed and fasted state.
在健康受试者中研究了高脂餐对盐酸哌甲酯渗透控释制剂OROS（盐酸哌甲酯）药代动力学的影响。与空腹相比，进食后哌甲酯血浆平均峰浓度出现时间稍晚，且哌甲酯血浆峰浓度和AUC值略高（约10 - 30%）。进食和空腹状态下哌甲酯的血浆消除半衰期无差异。同样，哌甲酯主要代谢产物α-苯基-2-哌啶乙酸（PPA；利他林酸）的峰浓度和AUC值在进食时比空腹时略高。18毫克剂量的C(max)治疗比（进食/空腹）的90%置信区间（CI）为120.6% - 140.0%，36毫克剂量为105.4 - 119.3%。18毫克剂量的AUC(infinity)治疗比的90% CI为114.6 - 125.7%，36毫克剂量为115.1 - 124.6%。服用18毫克剂量后测量了PPA水平，C(max)治疗比的90% CI为106.8 - 115.4%，AUC(infinity)为97.9 - 103.6%。这些结果表明进食时OROS（盐酸哌甲酯）不存在剂量倾泻。食物不影响药物吸收，OROS（盐酸哌甲酯）可在进食或空腹状态下给药。进食和空腹状态下不良事件谱无差异。
