Bastiaans Diane E T, Forcat Silvia, Lyall Hermione, Cressey Tim R, Hansudewechakul Rawiwan, Kanjanavanit Suparat, Noguera-Julian Antoni, Königs Christoph, Inshaw Jamie R J, Chalermpantmetagul Suwalai, Saïdi Yacine, Compagnucci Alexandra, Harper Lynda M, Giaquinto Carlo, Colbers Angela P H, Burger David M
From the *Department of Pharmacy, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; †MRC, Clinical Trials Unit, London, United Kingdom; ‡Imperial College Healthcare NHS Trust, Department of Pediatrics, St Mary's Hospital, London, United Kingdom; §Program for HIV Prevention and Treatment/IRD UMI-174, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; ¶Department of Pediatrics, Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand; ‖Department of Pediatrics, Nakornping Hospital, Chiang Mai, Thailand; **Unitat d´Infectologia, Servei de Pediatria, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain; ††Department of Pediatrics and Adolescent Medicine, J.W. Goethe University, Frankfurt, Germany; ‡‡INSERM, SC10-US19, Villejuif, France; and §§Department of Pediatrics, University of Padova, Italy.
Pediatr Infect Dis J. 2014 Mar;33(3):301-5. doi: 10.1097/INF.0000000000000014.
Lopinavir/ritonavir (LPV/r) pediatric tablets (100/25 mg) are approved by the United States Food and Drug Administration (FDA) and European Medicines Agency (EMA) as part of combination antiretroviral therapy. Dosing is based on body weight bands or body surface area under FDA approval and only body surface area by the EMA. This can lead to a different recommended dose. In addition, weight band-based dosing has not been formally studied in the target population. We evaluated the pharmacokinetics (PK) of LPV/r in children, administered twice daily according to the FDA weight bands, using pediatric tablets.
Fifty-three HIV-infected children were included in the PK substudy of the Paediatric European Network for the Treatment of AIDS 18 trial (KONCERT). In this study, children were randomized to receive LPV/r twice or once daily, according to FDA weight bands. A PK assessment was performed in 17, 16 and 20 children in the 15-25 kg, ≥ 25-35 kg and >35 kg weight band, respectively, while children took the tablets twice daily. Rich sampling was performed, and PK parameters were calculated by noncompartmental analysis. Given the high percentage of Asian children, it was also tested whether there was a difference in PK parameters between Asian and non-Asian children.
For the total group, LPV geometric mean AUC0-12, Cmax and C12 were 106.9 h × mg/L, 12.0 mg/L and 4.9 mg/L, respectively. There were no significant differences in LPV PK parameters between the weight bands. In addition, weight was not found to be associated with variability in Cmax, C12 or AUC0-12 for the LPV PK parameters.
FDA weight band-based dosing recommendations provide adequate exposure to LPV when using LPV/r pediatric tablets.
洛匹那韦/利托那韦（LPV/r）儿科片剂（100/25毫克）已获美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）批准，作为抗逆转录病毒联合疗法的一部分。根据FDA的批准，给药基于体重范围或体表面积，而EMA仅依据体表面积。这可能导致推荐剂量不同。此外，基于体重范围的给药尚未在目标人群中进行正式研究。我们评估了按照FDA体重范围每日两次给药的LPV/r儿科片剂在儿童中的药代动力学（PK）情况。
五十三名感染HIV的儿童纳入了欧洲儿科艾滋病治疗网络18试验（KONCERT）的PK子研究。在本研究中，儿童根据FDA体重范围被随机分配接受LPV/r每日两次或一次给药。在体重范围为15 - 25千克、≥25 - 35千克和>35千克的儿童中，分别有17名、16名和20名儿童在每日服用两次片剂时进行了PK评估。进行了密集采样，并通过非房室分析计算PK参数。鉴于亚洲儿童比例较高，还测试了亚洲儿童与非亚洲儿童之间PK参数是否存在差异。
对于整个组，LPV的几何平均AUC0 - 12、Cmax和C12分别为106.9小时×毫克/升、12.0毫克/升和4.9毫克/升。体重范围之间的LPV PK参数无显著差异。此外，未发现体重与LPV PK参数的Cmax、C12或AUC0 - 12的变异性相关。
当使用LPV/r儿科片剂时，基于FDA体重范围的给药建议可使LPV达到足够暴露量。
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