Patrick Kennerly S, González Mario A, Straughn Arthur B, Markowitz John S
Medical University of South Carolina, Department of Pharmaceutical Sciences, 280 Calhoun St., QF221A, Charleston, SC 29425-0742, USA.
Expert Opin Drug Deliv. 2005 Jan;2(1):121-43. doi: 10.1517/17425247.2.1.121.
dl-Methylphenidate (MPH) remains the most widely used pharmacological agent in the treatment of attention-deficit/hyperactivity disorder (ADHD). The predominantly dopaminergic mechanism of the psychostimulant actions has become more clearly defined. Neuroimaging and genetic studies are revealing the underlying neuropathology in ADHD. Novel extended-release (ER) MPH formulations now offer drug delivery options to overcome both the short-term actions of immediate-release (IR) MPH and the acute tolerance associated with the first-generation ER-MPH products. These novel MPH products apply proprietary technologies such as OROS (Alza), Diffucaps (Eurand) and SODAS (Elan) to offer both the convenience of once-a-day administration and absorption profiles resembling, to varying degrees, the standard multiple dose schedules of IR-MPH. The pharmacodynamics of the separate MPH enantiomers is in the process of further neuropharmacological characterisation. It is well established that dl-MPH undergoes marked stereoselective metabolism. Although l-MPH exhibits only minimal oral absorption, it may preferentially penetrate the brain, and interacts with ethanol to form the metabolite ethylphenidate. The newly approved resolved enantiomer product d-MPH is now available in an IR formulation, and when administered at one-half the dose to that of the racemate, is purported to produce a longer duration of clinical effect, despite essentially identical pharmacokinetics. A long-acting formulation of d-MPH, which employs the SODAS technology, is in the advanced stages of clinical development.
消旋甲基苯丙胺（MPH）仍然是治疗注意力缺陷多动障碍（ADHD）最广泛使用的药物。精神兴奋剂作用的主要多巴胺能机制已变得更加明确。神经影像学和遗传学研究正在揭示ADHD的潜在神经病理学。新型缓释（ER）MPH制剂现在提供了药物递送选择，以克服速释（IR）MPH的短期作用以及与第一代ER-MPH产品相关的急性耐受性。这些新型MPH产品应用了诸如OROS（阿尔扎公司）、Diffucaps（欧然德公司）和SODAS（伊兰公司）等专有技术，既提供了每日一次给药的便利性，又提供了在不同程度上类似于IR-MPH标准多剂量方案的吸收曲线。单独的MPH对映体的药效学正处于进一步神经药理学表征的过程中。众所周知，消旋MPH会发生显著的立体选择性代谢。虽然左旋MPH口服吸收极少，但它可能优先穿透大脑，并与乙醇相互作用形成代谢物乙基苯丙胺。新批准的拆分对映体产品右旋MPH现在有IR制剂，当以消旋体剂量的一半给药时，据称能产生更长的临床效应持续时间，尽管其药代动力学基本相同。一种采用SODAS技术的长效右旋MPH制剂正处于临床开发的后期阶段。
