Pharmacy Department, Royal Brompton Hospital, London, UK.
National Heart and Lung Institute, Imperial College London, London, UK.
J Antimicrob Chemother. 2021 Nov 12;76(12):3247-3254. doi: 10.1093/jac/dkab312.
To investigate the population pharmacokinetics of posaconazole gastroresistant tablets in children with cystic fibrosis (CF) and perform simulations to recommend optimal doses.
Children from a paediatric CF centre who had received posaconazole tablets and underwent therapeutic drug monitoring were identified from pharmacy records. Relevant clinical data were collated from case notes and electronic patient records and used to develop an allometrically scaled population pharmacokinetic model. A stepwise covariate model-building exercise evaluated the influence of interacting medicines and liver function.
One hundred posaconazole serum concentrations were collected from 37 children with a median age of 14 years (range 7-17). Posaconazole pharmacokinetics were adequately described by a one-compartment model with inter-individual variability on clearance. Dose simulations demonstrated a 77%-83% probability of attaining a trough target of 1 mg/L with a dose of 300 mg every 12 h for two doses then 300 mg once daily (OD) in children aged 6-11 years; and 86%-88% with a dose of 400 mg every 12 h for two doses then 400 mg OD in adolescents aged 12-17 years. This dose scheme also yielded a 90% probability of achieving an AUC of 30 mg·h/L. AUC and trough concentration were highly correlated (r2 = 0.98). Simulations showed that trough concentrations of >0.75 mg/L would exceed an AUC of 30 mg·h/L in 90% of patients.
A starting dose of 300 mg OD in those aged 6-11 years and 400 mg OD in those aged 12-17 years (following loading doses) yields a 90% probability of attaining an AUC of 30 mg·h/L.
研究囊性纤维化（CF）儿童中泊沙康唑肠溶片的群体药代动力学，并进行模拟以推荐最佳剂量。
从药房记录中确定了在儿科 CF 中心接受泊沙康唑片剂治疗并进行治疗药物监测的儿童患者。从病历和电子患者记录中收集了相关临床数据，并用于开发按比例缩放的群体药代动力学模型。逐步的协变量模型构建练习评估了相互作用药物和肝功能的影响。
从 37 名儿童中收集了 100 个泊沙康唑血清浓度，中位年龄为 14 岁（范围 7-17 岁）。泊沙康唑药代动力学通过具有清除率个体间变异的单室模型得到很好的描述。剂量模拟表明，对于年龄在 6-11 岁的儿童，剂量为 300mg 每 12 小时两次，然后每天 300mg（OD）；对于年龄在 12-17 岁的青少年，剂量为 400mg 每 12 小时两次，然后每天 400mg OD，达到 1mg/L 谷浓度目标的可能性为 77%-83%。该剂量方案也可使 AUC 达到 30mg·h/L 的概率为 90%。AUC 和谷浓度高度相关（r2=0.98）。模拟结果表明，超过 0.75mg/L 的谷浓度将使 90%的患者 AUC 超过 30mg·h/L。
年龄在 6-11 岁的儿童起始剂量为 300mg OD，年龄在 12-17 岁的儿童起始剂量为 400mg OD（在负荷剂量后），AUC 达到 30mg·h/L 的概率为 90%。
