From Product Development, Noven Pharmaceuticals, Inc, Jersey City, NJ.
Hisamitsu Pharmaceutical Co, Inc, Chiyoda-ku, Tokyo, Japan.
J Clin Psychopharmacol. 2021;41(3):286-294. doi: 10.1097/JCP.0000000000001383.
PURPOSE/BACKGROUND: The asenapine transdermal system (HP-3070) is the first antipsychotic patch approved in the United States for treatment of adults with schizophrenia.
METHODS/PROCEDURES: Three phase 1, open-label, randomized studies characterized the pharmacokinetic (PK) profile of HP-3070 by assessing its relative bioavailability compared with sublingual asenapine, its single-/multiple-dose PK and dose proportionality, and the effects of application site, ethnicity, and external heat on bioavailability. Two studies were conducted in healthy subjects, and 1 was conducted in adults with schizophrenia.
FINDINGS/RESULTS: During single HP-3070 administration, asenapine concentrations increased gradually over approximately 12 hours and remained steady until the patch was removed 24 hours after application. Asenapine area under the curve values at HP-3070 3.8 and 7.6 mg/24 hours doses were similar to those for sublingual asenapine 5 and 10 mg twice-daily doses, respectively, whereas peak exposure (maximum observed plasma concentration) was significantly lower. During daily application of HP-3070, steady-state PK was reached within approximately 72 hours after initiating daily dosing and was characterized by peak-to-trough asenapine plasma concentration ratio of approximately 1.5. HP-3070 PK was dose proportional in the dose range studied, not affected by administration site, and similar across the studied ethnic groups. Application of external heat increased the rate of asenapine absorption (time to reach maximum observed plasma concentration) but did not significantly affect peak and total exposure.
IMPLICATIONS/CONCLUSIONS: HP-3070 exhibited a dose-dependent PK profile unaffected by site of administration or ethnicity. HP-3070 showed a predictable absorption profile with limited variability, with an area under the curve similar to that of sublingual asenapine. Based on these PK metrics, HP-3070 steadily delivers asenapine with lower peaks and troughs than sublingual administration of asenapine.
目的/背景：阿塞那平透皮贴剂（HP-3070）是美国批准的第一种用于治疗精神分裂症成人的抗精神病贴片。
方法/程序：三项 1 期、开放性、随机研究通过评估其与舌下含服阿塞那平相比的相对生物利用度、单次/多次剂量药代动力学和剂量比例性，以及应用部位、种族和外部热量对生物利用度的影响，描述了 HP-3070 的药代动力学（PK）特征。两项研究在健康受试者中进行，一项在精神分裂症成人中进行。
结果/发现：在单次 HP-3070 给药期间，阿塞那平浓度在大约 12 小时内逐渐增加，直到应用 24 小时后贴片被移除时才保持稳定。HP-3070 3.8 和 7.6mg/24 小时剂量的阿塞那平曲线下面积值与舌下含服阿塞那平 5 和 10mg 每日两次剂量相似，而峰暴露（最大观察到的血浆浓度）明显较低。在每日应用 HP-3070 期间，在开始每日给药后大约 72 小时内达到稳态 PK，并以约 1.5 的峰谷阿塞那平血浆浓度比为特征。在研究的剂量范围内，HP-3070 的 PK 呈剂量比例关系，不受给药部位的影响，并且在研究的种族群体中相似。应用外部热量会增加阿塞那平吸收的速度（达到最大观察到的血浆浓度的时间），但对峰和总暴露没有显著影响。
意义/结论：HP-3070 表现出剂量依赖性 PK 特征，不受给药部位或种族的影响。HP-3070 显示出可预测的吸收曲线，变异性有限，曲线下面积与舌下含服阿塞那平相似。基于这些 PK 指标，HP-3070 以低于舌下含服阿塞那平的峰谷值稳定地输送阿塞那平。
