Eden Mental Health Centre, Winkler, Manitoba, Canada.
Purdue Pharma L.P., Stamford, CT.
J Clin Psychopharmacol. 2020 Nov/Dec;40(6):579-587. doi: 10.1097/JCP.0000000000001277.
PURPOSE/BACKGROUND: PRC-063 is a once-daily, extended-release oral formulation of methylphenidate hydrochloride developed to provide early and prolonged symptom improvement in patients with attention-deficit/hyperactivity disorder.
METHODS/PROCEDURES: We conducted 3 randomized, open-label crossover studies of the pharmacokinetics of PRC-063 in healthy, nonobese men and women aged 18 to 45 years. PRC-063 (100 mg/d) was compared with immediate-release methylphenidate (20 mg, 3 times daily) when administered on a single day under fasted and fed conditions and at steady state (day 5 of repeat dosing under fasted conditions). The pharmacokinetics of PRC-063 administered as capsule contents sprinkled on apple sauce, yoghurt, or ice cream were also investigated.
FINDINGS/RESULTS: PRC-063 demonstrated biphasic absorption, with 2 distinct peak plasma concentrations. Intake of a high-fat, high-calorie meal did not increase the peak plasma methylphenidate concentration (Cmax) or extent of absorption (area under the curve), however; it resulted in slower uptake versus a fasted state. During repeated dosing, steady state was reached with no further accumulation of methylphenidate from day 3. At steady state, PRC-063 gave higher evening and trough plasma methylphenidate levels than immediate-release methylphenidate (3 times daily). The pharmacokinetics of PRC-063 sprinkled on food were comparable to that of intact capsules. Reported adverse events (AEs) were consistent with the established safety profile of methylphenidate. There were no serious AEs, but 3 subjects discontinued the repeat-dosing study because of AEs assessed as possibly related to study treatment.
IMPLICATIONS/CONCLUSIONS: Our data indicate that PRC-063 can be taken with or without food or by sprinkling capsule contents on food.
目的/背景：PRC-063 是一种每日一次的盐酸哌甲酯延长释放口服制剂，旨在为注意力缺陷/多动障碍患者提供早期和持久的症状改善。
方法/程序：我们进行了 3 项随机、开放标签的 PRC-063 药代动力学交叉研究，纳入了年龄在 18 至 45 岁的健康、非肥胖男性和女性。PRC-063（100mg/d）与速释哌甲酯（20mg，每日 3 次）进行比较，在禁食和进食条件下单日给药，以及在禁食条件下重复给药第 5 天的稳态时给药。还研究了 PRC-063 胶囊内容物撒在苹果酱、酸奶或冰淇淋上给药的药代动力学。
结果/发现：PRC-063 表现出双相吸收，有 2 个明显的血浆峰浓度。摄入高脂肪、高热量膳食不会增加血浆哌甲酯的峰浓度（Cmax）或吸收程度（曲线下面积）；但与禁食状态相比，它会导致吸收速度减慢。重复给药时，从第 3 天开始，哌甲酯达到稳态，没有进一步积累。在稳态时，PRC-063 比速释哌甲酯（每日 3 次）产生更高的傍晚和谷值血浆哌甲酯水平。撒在食物上的 PRC-063 的药代动力学与完整胶囊相似。报告的不良事件（AE）与哌甲酯的既定安全性特征一致。没有严重的 AE，但 3 名受试者因评估为可能与研究治疗相关的 AE 而退出重复给药研究。
意义/结论：我们的数据表明，PRC-063 可以在进食或不进食时服用，也可以将胶囊内容物撒在食物上服用。
