Abbas Richat, Palumbo Donna, Walters Faith, Belden Heidi, Berry Sally A
Pfizer Inc, New York, New York.
Pfizer Inc, New York, New York.
Clin Ther. 2016 May;38(5):1151-7. doi: 10.1016/j.clinthera.2016.02.026. Epub 2016 Mar 24.
A novel methylphenidate hydrochloride extended-release chewable tablet (MPH ERCT) was developed to potentially address an unmet need for patients with attention-deficit/hyperactivity disorder, especially children, who cannot or will not swallow tablets or would prefer the convenience of a chewable tablet. This randomized, open-label, crossover trial compared the pharmacokinetic properties and relative bioavailability of MPH ERCT with an MPH chewable immediate-release tablet (IR MPH) formulation in healthy adults.
Healthy men and women 18 to 55 years of age were randomly assigned to MPH ERCT 40 mg or 40 mg IR MPH administered in 2 equal doses of 20 mg 6 hours apart with a 7-day washout period. Plasma concentrations of MPH at selected time points up to 24 hours were measured, and pharmacokinetic parameters were determined using a noncompartmental approach in the SAS (Version 9.2) PROC general linear model procedure.
A total of 33 participants were enrolled in the study; 31 participants were included in the pharmacokinetic analysis. The exposure ratios for MPH ERCT and IR MPH (MPH ERCT/IR MPH) for area under the analyte concentration versus time curves (AUC) from time zero to the last measurable analyte concentration (AUC0-last) (87.64%; 95% CI, 84.96-90.41) and AUC0-∞ (89.11%; 95% CI, 86.57-91.73) were within the standard 80% to 125% bioequivalence acceptance criteria. Mean Cmax for MPH ERCT and IR MPH was 12.51 ng/mL and 15.57 ng/mL, respectively; mean time to Cmax was 4.16 hours and 6.43 hours, respectively. The mean Cmax of MPH ERCT was 80% of the Cmax of IR MPH due to a higher peak concentration that occurs after the second dose of IR MPH. All adverse events were mild in severity.
The relative bioavailability of MPH ERCT 40 mg, based on the exposure (AUC), was comparable to that of IR MPH 40 mg administered in 2 equal doses of 20 mg 6 hours apart. Both formulations were generally well tolerated.
开发一种新型盐酸哌甲酯缓释咀嚼片（MPH ERCT），以满足注意力缺陷多动障碍患者，尤其是儿童的未被满足的需求，这些患者不能或不愿吞咽片剂，或者更喜欢咀嚼片的便利性。这项随机、开放标签、交叉试验比较了MPH ERCT与MPH咀嚼速释片（IR MPH）制剂在健康成年人中的药代动力学特性和相对生物利用度。
将18至55岁的健康男性和女性随机分配至MPH ERCT 40 mg组或40 mg IR MPH组，均以20 mg的等剂量分两次给药，间隔6小时，洗脱期为7天。在长达24小时的选定时间点测量MPH的血浆浓度，并使用SAS（版本9.2）PROC通用线性模型程序中的非房室方法确定药代动力学参数。
共有33名参与者纳入研究；31名参与者纳入药代动力学分析。MPH ERCT和IR MPH的暴露比（MPH ERCT/IR MPH），即从时间零点至最后可测量分析物浓度的分析物浓度-时间曲线下面积（AUC）（AUC0-last）（87.64%；95%CI，84.96 - 90.41）和AUC0-∞（89.11%；95%CI，86.57 - 91.73）在标准的80%至125%生物等效性接受标准范围内。MPH ERCT和IR MPH的平均Cmax分别为12.51 ng/mL和15.57 ng/mL；达到Cmax的平均时间分别为4.16小时和6.43小时。由于第二次服用IR MPH后出现更高的峰值浓度，MPH ERCT的平均Cmax为IR MPH的Cmax的80%。所有不良事件的严重程度均为轻度。
基于暴露量（AUC），40 mg MPH ERCT的相对生物利用度与间隔6小时分两次给予20 mg的40 mg IR MPH相当。两种制剂总体耐受性良好。
