Braeburn Pharmaceuticals, Princeton, NJ, USA.
Clin Pharmacol Drug Dev. 2018 Mar;7(3):298-310. doi: 10.1002/cpdd.428. Epub 2018 Feb 8.
A subcutaneous risperidone implant (RI) formulation was developed to improve medication adherence in schizophrenia. Two phase 1 studies were conducted to evaluate the pharmacokinetics of RI in adult patients with schizophrenia. In study 1, all subjects were stable on 4 mg oral risperidone; subsequently, the first subject received 375 mg RI for 1 month, and the remaining subjects received 375 mg RI for 3 months. In study 2, all subjects were stable on oral risperidone 4 mg, 6 mg, or 8 mg and subsequently received RI 480 mg, 720 mg, or 960 mg, respectively, for 6 months. Blood samples were collected at prespecified time points. Various pharmacokinetic parameters were determined in both studies. In both studies risperidone total active moiety plasma concentrations following RI increased slowly, reached therapeutic levels within approximately 2 days, and remained relatively stable. In study 1, the average concentration for RI was 81.3% of the oral trough concentration and 27.5% of the oral peak concentration. In study 2, the steady-state concentration for RI was comparable to the oral trough concentration of the corresponding dose. Patient disease status remained stable with no major safety issues. RI may represent an alternative formulation for schizophrenia treatment with a lower peak-to-trough plasma drug ratio than oral risperidone.
一种皮下利培酮植入剂（RI）被开发出来，以提高精神分裂症患者的用药依从性。进行了两项 1 期研究，以评估 RI 在成人精神分裂症患者中的药代动力学。在研究 1 中，所有受试者均稳定服用 4 毫克口服利培酮；随后，第一名受试者接受 375 毫克 RI 治疗 1 个月，其余受试者接受 375 毫克 RI 治疗 3 个月。在研究 2 中，所有受试者均稳定服用 4 毫克、6 毫克或 8 毫克口服利培酮，随后分别接受 RI 480 毫克、720 毫克或 960 毫克治疗 6 个月。在预定时间点采集血样。在两项研究中均确定了各种药代动力学参数。在两项研究中，RI 后利培酮总活性部分的血浆浓度增加缓慢，大约 2 天内达到治疗水平，并保持相对稳定。在研究 1 中，RI 的平均浓度为口服谷浓度的 81.3%和口服峰浓度的 27.5%。在研究 2 中，RI 的稳态浓度与相应剂量的口服谷浓度相当。患者病情稳定，无重大安全问题。RI 可能代表一种治疗精神分裂症的替代制剂，其峰谷血浆药物比值低于口服利培酮。
