Division of Janssen Pharmaceutica NV, Janssen Research & Development, Beerse, Belgium.
Janssen Research & Development, LLC, Raritan, NJ, USA.
Clin Pharmacol Drug Dev. 2015 Jul;4(4):270-8. doi: 10.1002/cpdd.144. Epub 2014 Aug 28.
Paliperidone palmitate (PP) is a once-monthly long-acting injectable antipsychotic approved for the treatment of schizophrenia in many countries. To evaluate the different injection-site options, we compared the pharmacokinetic profile of paliperidone after multiple injections of PP 100 mg eq. (156 mg of PP, equivalent to 100 mg of paliperidone) on days 1, 8, 36, and 64 into the deltoid (n = 24) or gluteal muscle (n = 25) in patients with schizophrenia. After four injections in the deltoid muscle, paliperidone exposure was higher for AUCτ and Cmax , compared with the gluteal muscle (geometric mean AUCτ -based ratio: 120% [90% CI: 93.1-154.7%], and geometric mean Cmax -based ratio: 130% [90% CI: 100.6-168.9%]). The mean [SD] fluctuation index was higher, with a larger interpatient variability, after deltoid-injections (75.9% [30.9%]) than gluteal-injections (58.5% [14.3%]). The median tmax was similar for both sites. PP was generally tolerable in patients, with more favorable local-site tolerability for gluteal-injection. In conclusion, to achieve therapeutic-concentrations quickly, the first-two injections of PP are best administered into the deltoid muscle, whereas thereafter maintenance-injections can be administered either in the deltoid or gluteal muscle.
棕榈酸帕利哌酮（PP）是一种每月一次的长效注射用抗精神病药，已在许多国家获得批准，用于治疗精神分裂症。为了评估不同的注射部位选择，我们比较了精神分裂症患者第 1、8、36 和 64 天接受 100mgPP（156mgPP，相当于 100mg 帕利哌酮）的肩胛下肌（n=24）或臀肌（n=25）4 次多剂量注射后的药代动力学特征。与臀肌相比，肩胛下肌 4 次注射后，AUCτ和 Cmax的帕利哌酮暴露量更高（基于几何均数 AUCτ的比值：120%[90%置信区间：93.1-154.7%]，基于几何均数 Cmax的比值：130%[90%置信区间：100.6-168.9%]）。肩胛下肌注射后的波动指数较高，个体间差异较大（75.9%[30.9%]），而臀肌注射后的波动指数较小（58.5%[14.3%]）。两种部位的中位 tmax 相似。患者对 PP 总体耐受良好，臀肌注射的局部耐受性更好。总之，为了快速达到治疗浓度，PP 的前两次注射最好在肩胛下肌进行，而之后的维持注射可以在肩胛下肌或臀肌进行。
