Hanan Nathan John, Paul Mary Elizabeth, Huo Yanling, Kapetanovic Suad, Smith Elizabeth, Siberry George, Brouwers Pim, Graham Bobbie, Johnston Benjamin, Capparelli Edmund V, Best Brookie M
Department of Pediatrics-Rady Children's Hospital San Diego, University of California, San Diego, San Diego, CA, United States.
Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States.
Front Pediatr. 2019 Feb 6;7:16. doi: 10.3389/fped.2019.00016. eCollection 2019.
Due to potential disease and drug interactions, the appropriate sertraline starting dose and titration range may require adjustment in pediatric patients living with HIV. This is the first report of sertraline pharmacokinetics in HIV-infected youth. IMPAACT P1080 was a multicenter pilot study describing psychiatric medication pharmacokinetics in HIV-infected and uninfected youth. Participants were stable on sertraline, >6 to <25 years old, and (1) HIV-uninfected (HIV(-)), (2) HIV-infected taking efavirenz (EFV), or (3) HIV-infected taking boosting ritonavir/protease inhibitor (PI/r). Sampling occurred at pre-dose, 2, 4, 6, 12, and 24-h post-dose. Analyses were performed for sertraline and N-desmethylsertraline, and CYP2D6 phenotyping was completed with dextromethorphan. Thirty-one participants (16 HIV(-), 12 PI/r, and 3 EFV) had median (range) weight, age, and dose of 69.5 (31.5-118.2) kg, 21.8 (9.1-24.7) years, and 75.0 (12.5-150.0) mg once daily. Sertraline exposure was highest for HIV(-) and lowest for EFV cohorts; median dose-normalized was 1176 (HIV(-)), 791 (PI/r) and 473 (EFV) nghr/mL, and C was 32.7 (HIV(-)), 20.1 (PI/r), and 12.8 (EFV) ng/mL. The urinary dextromethorphan/dextrorphan (DXM/DXO) ratio was higher in HIV(-) vs. PI/r cohorts ( = 0.01). Four HIV(-) participants were CYP2D6 poor metabolizers (ln(DXM/DXO) of >-0.5). HIV(-) cohort had the highest sertraline exposure. Sertraline exposure was ~40% lower in the PI/r cohort than in HIV(-); the need to alter sertraline dose ranges for PI/r participants is not clear. The impact of efavirenz on sertraline needs further investigation due to limited numbers of EFV participants.
由于潜在的疾病和药物相互作用，对于感染HIV的儿科患者，舍曲林的合适起始剂量和滴定范围可能需要调整。这是关于HIV感染青少年中舍曲林药代动力学的首份报告。IMPAACT P1080是一项多中心试点研究，描述了HIV感染和未感染青少年的精神科药物药代动力学。参与者年龄在>6至<25岁之间，且舍曲林治疗稳定，分为三组：(1)未感染HIV（HIV(-)）；(2)感染HIV且服用依非韦伦（EFV）；(3)感染HIV且服用增效利托那韦/蛋白酶抑制剂（PI/r）。在给药前、给药后2、4、6、12和24小时进行采样。对舍曲林和N-去甲基舍曲林进行分析，并用右美沙芬完成CYP2D6表型分析。31名参与者（16名HIV(-)、12名PI/r和3名EFV）的体重、年龄和剂量中位数（范围）分别为69.5（31.5 - 118.2）kg、21.8（9.1 - 24.7）岁和75.0（12.5 - 150.0）mg/日。舍曲林暴露量在HIV(-)组中最高，在EFV组中最低；剂量标准化后的中位数AUC为1176（HIV(-)）、791（PI/r）和473（EFV）ng·hr/mL，Cmax为32.7（HIV(-)）、20.1（PI/r）和12.8（EFV）ng/mL。HIV(-)组的尿右美沙芬/右啡烷（DXM/DXO）比值高于PI/r组（P = 0.01）。4名HIV(-)参与者为CYP2D6慢代谢者（ln(DXM/DXO)> - 0.5）。HIV(-)组的舍曲林暴露量最高。PI/r组的舍曲林暴露量比HIV(-)组低约40%；对于PI/r参与者是否需要改变舍曲林剂量范围尚不清楚。由于EFV参与者数量有限，依非韦伦对舍曲林的影响需要进一步研究。
