Martin Patrick, Dirks Bryan, Gertsik Lev, Walling David, Stevenson Annette, Corcoran Mary, Raychaudhuri Aparna, Ermer James
From the *Shire Development LLC, Wayne, PA; †California Clinical Trials Medical Group, Glendale; and ‡Collaborative Neuroscience Network, Garden Grove, CA.
J Clin Psychopharmacol. 2014 Dec;34(6):682-9. doi: 10.1097/JCP.0000000000000205.
To assess the safety and pharmacokinetics of lisdexamfetamine dimesylate (LDX), a d-amphetamine prodrug, this double-blind study enrolled adults with clinically stable schizophrenia who were adherent (≥12 weeks) to antipsychotic pharmacotherapy. The participants received placebo or ascending LDX doses (50, 70, 100, 150, 200, and 250 mg) daily for 5 days at each dose (dose periods, 1-6; days, 1-5). Of the 31 enrolled participants, 27 completed the study (placebo, n = 6; LDX, n = 21). Treatment-emergent adverse events (AEs) were reported by 4 participants receiving placebo and by 23 participants receiving LDX (all doses) with no serious AEs while on active treatment. For all periods, the mean postdose change on day 5 (up to 12 hours postdose) in systolic and diastolic blood pressure and pulse, respectively, ranged from -4.62 to 8.05 mm Hg, -3.67 to 4.43 mm Hg, and -3.57 to 14.43 beats per minute for placebo and -3.83 to 11.25 mm Hg, -1.55 to 5.80 mm Hg, and -0.36 to 21.26 beats per minute for LDX. With ascending LDX dose, the mean (SD) maximum plasma concentration for LDX-derived d-amphetamine ranged from 51.68 (10.28) to 266.27 (56.55) ng/mL. The area under the plasma concentration-time curve for 24 hours ranged from 801.8 (170.2) to 4397.9 (1085.9) ng[BULLET OPERATOR]h/mL. The d-amphetamine maximum plasma concentration and area under the plasma concentration-time curve increased linearly with ascending LDX dose. Antipsychotic agents did not markedly affect d-amphetamine pharmacokinetics. Over a wide range of ascending doses, LDX safety profile in adults with schizophrenia was consistent with previous findings with no unexpected treatment-emergent AEs. Pulse tended to increase with LDX dose; overall, blood pressure did not increase with LDX dose. Consistent with previous studies, pharmacokinetic parameters increased linearly with increasing LDX dose.
为评估二甲基磺酸赖右苯丙胺（LDX，一种右旋苯丙胺前体药物）的安全性和药代动力学，这项双盲研究纳入了临床病情稳定且已坚持（≥12周）抗精神病药物治疗的成年精神分裂症患者。参与者接受安慰剂或递增剂量的LDX（50、70、100、150、200和250毫克），每种剂量每日服用5天（剂量期1 - 6；天数1 - 5）。在31名入组参与者中，27名完成了研究（安慰剂组，n = 6；LDX组，n = 21）。4名接受安慰剂的参与者和23名接受LDX（所有剂量）的参与者报告了治疗中出现的不良事件（AE），在接受活性治疗期间均无严重不良事件。在所有阶段，安慰剂组在第5天（给药后长达12小时）收缩压、舒张压和脉搏的平均给药后变化分别为-4.62至8.05毫米汞柱、-3.67至4.43毫米汞柱和-3.57至14.43次/分钟，而LDX组分别为-3.83至11.25毫米汞柱、-1.55至5.80毫米汞柱和-0.36至21.26次/分钟。随着LDX剂量的增加，LDX衍生的右旋苯丙胺的平均（标准差）最大血浆浓度范围为51.68（10.28）至266.27（56.55）纳克/毫升。24小时血浆浓度-时间曲线下面积范围为801.8（170.2）至4397.9（1085.9）纳克·小时/毫升。右旋苯丙胺的最大血浆浓度和血浆浓度-时间曲线下面积随LDX剂量的增加呈线性增加。抗精神病药物对右旋苯丙胺的药代动力学没有明显影响。在广泛的递增剂量范围内，LDX在成年精神分裂症患者中的安全性与先前的研究结果一致，没有出现意外的治疗中出现的不良事件。脉搏倾向于随LDX剂量增加；总体而言，血压并未随LDX剂量升高。与先前的研究一致，药代动力学参数随LDX剂量增加呈线性增加。
