Clinical Pharmacology Group, Clinical Research, Drug Development Division, Sumitomo Dainippon Pharma Co., Ltd., Tokyo, Japan.
Department of Neuropsychiatry, Nippon Medical School, Tokyo, Japan.
Int J Neuropsychopharmacol. 2021 Feb 15;24(2):108-117. doi: 10.1093/ijnp/pyaa071.
Transdermal antipsychotic patch formulations offer potential benefits, including improved adherence. This study investigated the striatal dopamine D2 receptor occupancy with daily blonanserin transdermal patch application.
This open-label, phase II study enrolled 18 Japanese outpatients (20 to <65 years) with schizophrenia (DSM-IV-TR criteria; total Positive and Negative Syndrome Scale score <120 at screening) treated with blonanserin 8-mg or 16-mg tablets. Patients continued tablets for 2-4 weeks at their current dose and were then assigned to once-daily blonanserin patches (10/20/40/60/80 mg daily) for 2-4 weeks based on the oral dose. [11C]raclopride positron emission tomography scanning determined blonanserin striatal dopamine D2 receptor occupancy (primary endpoint). Secondary endpoints included assessment of receptor occupancy by dose, changes in Positive and Negative Syndrome Scale and Clinical Global Impressions-Severity of Illness-Severity scores, patient attitudes towards adherence, and patch adhesiveness.
Of 18 patients who started the blonanserin tablet treatment period, 14 patients completed treatment. Mean D2 receptor occupancy for blonanserin tablets 8 mg/d (59.2%, n = 5) and 16 mg/d (66.3%, n = 9) was within the values for blonanserin patches: 10 mg/d (33.3%, n = 3), 20 mg/d (29.9%, n = 2), 40 mg/d (61.2%, n = 3), 60 mg/d (59.0%, n = 3), and 80 mg/d (69.9%, n = 3). Occupancy generally increased with increasing blonanserin dose for both formulations with the half maximal receptor occupancy for tablets and patches associated with doses of 6.9 mg/d and 31.9 mg/d, respectively. Diurnal variability in occupancy was lower during transdermal patch treatment than during tablet treatment. Blonanserin transdermal patches were well tolerated with no major safety concerns.
Blonanserin patches (40/80 mg/d) have lower diurnal variability in occupancy than blonanserin tablets (8/16 mg/d), and patches at doses of 40 mg/d and 80 mg/d appear to be a suitable alternative for blonanserin tablets at doses of 8 mg/d and 16 mg/d, respectively. Blonanserin patches represent a potential new treatment option for patients with schizophrenia.
JAPIC Clinical Trials Information registry (www.clinicaltrials.jp; JapicCTI-No: JapicCTI-121914).
透皮抗精神病贴片制剂具有改善依从性等潜在优势。本研究旨在探讨每日使用苯丁酸钠透皮贴片对纹状体多巴胺 D2 受体占有率的影响。
这是一项开放标签、II 期研究，共纳入 18 名日本门诊精神分裂症患者（DSM-IV-TR 标准；筛选时阳性和阴性综合征量表总分<120），接受苯丁酸钠 8mg 或 16mg 片剂治疗。患者在当前剂量下继续服用片剂 2-4 周，然后根据口服剂量，每天一次分配使用苯丁酸钠贴片（10/20/40/60/80mg 每日）2-4 周。[11C]raclopride 正电子发射断层扫描测定苯丁酸钠的纹状体多巴胺 D2 受体占有率（主要终点）。次要终点包括按剂量评估受体占有率、阳性和阴性综合征量表及临床总体印象-疾病严重程度-严重程度评分的变化、患者对依从性的态度以及贴片的粘性。
在开始苯丁酸钠片剂治疗期的 18 名患者中，有 14 名患者完成了治疗。苯丁酸钠 8mg/d（59.2%，n=5）和 16mg/d（66.3%，n=9）的 D2 受体占有率与苯丁酸钠贴片的数值一致：10mg/d（33.3%，n=3）、20mg/d（29.9%，n=2）、40mg/d（61.2%，n=3）、60mg/d（59.0%，n=3）和 80mg/d（69.9%，n=3）。两种制剂的受体占有率均随苯丁酸钠剂量的增加而增加，片剂和贴片的半最大受体占有率分别与 6.9mg/d 和 31.9mg/d 相关。与片剂治疗相比，透皮贴片治疗的日间变异较小。苯丁酸钠透皮贴片耐受性良好，无重大安全性问题。
苯丁酸钠贴片（40/80mg/d）的占有率日间变异较苯丁酸钠片剂（8/16mg/d）小，40mg/d 和 80mg/d 的贴片可能分别是 8mg/d 和 16mg/d 苯丁酸钠片剂的合适替代药物。苯丁酸钠贴片为精神分裂症患者提供了一种新的潜在治疗选择。
日本临床试验信息注册中心（www.clinicaltrials.jp；JapicCTI-No：JapicCTI-121914）。
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