Shire (a member of the Takeda Group of Companies), 300 Shire Way, Lexington, MA, 02421, USA.
Drugs R D. 2019 Jun;19(2):167-175. doi: 10.1007/s40268-019-0267-y.
SHP465 mixed amphetamine salts extended release is a once-daily, single-entity, mixed amphetamine salts capsule product for attention-deficit/hyperactivity disorder. The objective of this study was to evaluate amphetamine pharmacokinetics following SHP465 mixed amphetamine salts under three administration conditions.
Healthy adults (n = 16) enrolled in an open-label, randomized, three-period crossover study with three single-dose 50-mg SHP465 mixed amphetamine salts treatments (fasting ≥ 10 h before administration [reference]; high-fat meal consumption 30 min before administration; sprinkling capsule contents on applesauce) separated by ≥ 7-day washouts. Blood samples for evaluating d- and l-amphetamine pharmacokinetics were collected pre-dose and up to 60 h post-dose. Assessments included maximum plasma concentration, time to maximum plasma concentration, and area under the plasma concentration-time curve from 0 to infinity. Exponentiated least-squares mean ratios with 90% confidence intervals for test treatments relative to the reference treatment were calculated, with the absence of an effect indicated by the 90% confidence intervals falling within the 80-125% range.
Least-squares mean (90% confidence interval) ratios for maximum plasma concentration and area under the plasma concentration-time curve from 0 to infinity indicated neither consuming a high-fat meal (d-amphetamine: 85.33 [80.44, 90.50] and 91.11 [86.69, 95.75], respectively; l-amphetamine: 85.22 [80.18, 90.59] and 88.74 [83.89, 93.87]) nor sprinkling the capsule contents on applesauce (d-amphetamine: 95.76 [90.28, 101.57] and 95.77 [91.13, 100.65]; l-amphetamine: 96.90 [91.16, 103.00] and 94.78 [89.60, 100.26]) altered amphetamine exposure. Consuming a high-fat meal prolonged median time to maximum plasma concentration for d- and l-amphetamine by 5.0 and 4.5 h, respectively, relative to reference treatment.
These findings demonstrate SHP465 mixed amphetamine salts capsules can be swallowed whole with or without food or the capsule contents can be sprinkled on applesauce.
SHP465 混合安非他命盐长效释放胶囊是一种每日一次、单一实体的混合安非他命盐胶囊，用于治疗注意力缺陷/多动障碍。本研究的目的是评估 SHP465 混合安非他命盐在三种给药条件下的安非他命药代动力学。
健康成年人（n=16）参加了一项开放标签、随机、三周期交叉研究，接受了三种单次 50mg SHP465 混合安非他命盐治疗（禁食≥10 小时[参考]；给药前 30 分钟进食高脂肪餐；将胶囊内容物撒在苹果酱上），间隔≥7 天洗脱期。采集血样以评估 d-和 l-安非他命的药代动力学，采集时间为给药前和给药后 60 小时。评估包括最大血浆浓度、达峰时间和从 0 到无穷大的血浆浓度-时间曲线下面积。用试验治疗相对于参考治疗的指数最小二乘均值比值及其 90%置信区间进行计算，90%置信区间落在 80-125%范围内表示无影响。
最大血浆浓度和从 0 到无穷大的血浆浓度-时间曲线下面积的最小二乘均值（90%置信区间）比值表明，进食高脂肪餐（d-安非他命：85.33[80.44, 90.50]和 91.11[86.69, 95.75]）或将胶囊内容物撒在苹果酱上（d-安非他命：95.76[90.28, 101.57]和 95.77[91.13, 100.65]；l-安非他命：96.90[91.16, 103.00]和 94.78[89.60, 100.26]）并未改变安非他命的暴露量。与参考治疗相比，进食高脂肪餐使 d-和 l-安非他命的达峰时间中位数分别延长了 5.0 和 4.5 小时。
这些发现表明，SHP465 混合安非他命盐胶囊可以整片吞服，无论是否与食物同服，或者可以将胶囊内容物撒在苹果酱上。
