Angelini RR&D (Research Regulatory & Development), Angelini S.p.A., S. Palomba-Pomezia, Rome, Italy.
Simcyp Division, Certara UK, Sheffield, UK.
CPT Pharmacometrics Syst Pharmacol. 2020 Feb;9(2):77-86. doi: 10.1002/psp4.12480. Epub 2020 Jan 11.
There is a paucity of clinical trials for the treatment of pediatric insomnia. This study was designed to predict the doses of trazodone to guide dosing in a clinical trial for pediatric insomnia using physiologically-based pharmacokinetic (PBPK) modeling. Data on the pharmacokinetics of trazodone in children are currently lacking. The interaction potential between trazodone and atomoxetine was also predicted. Doses predicted in the following age groups, with exposures corresponding to adult dosages of 30, 75, and 150 mg once a day (q.d.), respectively, were: (i) 2- to 6-year-old group, doses of 0.35, 0.8, and 1.6 mg/kg q.d.; (ii) >6- to 12-year-old group, doses of 0.4, 1.0, and 1.9 mg/kg q.d.; (iii) >12- to 17-year-old group, doses of 0.4, 1.1, and 2.1 mg/kg q.d. An interaction between trazodone and atomoxetine was predicted to be unlikely. Clinical trials based on the aforementioned predicted dosing are currently in progress, and pharmacokinetic data obtained will enable further refinement of the PBPK models.
儿科失眠症的治疗方法临床试验较少。本研究旨在通过基于生理的药代动力学（PBPK）模型预测曲唑酮的剂量，以指导儿科失眠症的临床试验中的剂量。目前缺乏儿童曲唑酮药代动力学的数据。还预测了曲唑酮和托莫西汀之间的相互作用潜力。预测以下年龄段的剂量，暴露量分别对应于成人剂量 30、75 和 150mg 每天一次（qd），分别为：（i）2 至 6 岁组，剂量为 0.35、0.8 和 1.6mg/kg qd；（ii）6 至 12 岁组，剂量为 0.4、1.0 和 1.9mg/kg qd；（iii）12 至 17 岁组，剂量为 0.4、1.1 和 2.1mg/kg qd。预测曲唑酮和托莫西汀之间不太可能发生相互作用。基于上述预测剂量的临床试验目前正在进行中，获得的药代动力学数据将使 PBPK 模型得到进一步改进。
