Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093-0719, USA.
J Acquir Immune Defic Syndr. 2011 Dec 1;58(4):385-91. doi: 10.1097/QAI.0b013e318232b057.
Lopinavir/ritonavir (Kaletra) is first-line therapy for pediatric HIV infection. In clinical practice, Kaletra tablets are occasionally crushed for pediatric administration. This study compared lopinavir/ritonavir exposure between whole and crushed tablets in HIV-infected children.
This was a randomized, open-label, cross-over study of pediatric patients taking lopinavir/ritonavir as part of their antiretroviral regimen. Each subject had 2 separate (within 30 days) steady-state 12-hour pharmacokinetic (PK) studies with crushed and whole 200/50 mg lopinavir/ritonavir tablets.
PK blood samples were drawn at 0 (predose), 1, 2, 4, 6, 8, and 12 hours postdose. Lopinavir and ritonavir plasma concentrations measured by high-performance liquid chromatography were used to calculate non-compartmental area under the concentration versus time curve (AUC) and clearance. Wilcoxon signed-rank tests compared PK values between crushed and whole tablets.
Twelve children, median age of 13 years (10-16 years), took 550/138 mg·m(-2) per day lopinavir/ritonavir divided every 12 hours. The median lopinavir AUC after crushed and whole tablets were 92 mg·hr·L(-1) and 144 mg·hr·L(-1), respectively, with an AUC ratio of 0.55 (P = 0.003). Median ritonavir AUC of crushed and whole tablets were 7 mg·hr·L(-1) and 13.3 mg·hr·L(-1), respectively, with an AUC ratio of 0.53 (P = 0.006).
Administration of crushed 200/50 mg lopinavir/ritonavir tablets to children significantly reduced lopinavir and ritonavir exposure with a decrease in AUC by 45% and 47%, respectively. The administration of crushed tablets would require higher doses and therapeutic drug monitoring to ensure adequate lopinavir exposure in patients requiring this practice. The use of crushed lopinavir/ritonavir tablets should be avoided, if possible.
洛匹那韦/利托那韦（克力芝）是儿科 HIV 感染的一线治疗药物。在临床实践中，克力芝片剂偶尔会被压碎以供儿科使用。本研究比较了 HIV 感染儿童服用整粒和压碎片剂的洛匹那韦/利托那韦暴露情况。
这是一项针对接受洛匹那韦/利托那韦作为其抗逆转录病毒方案一部分的儿科患者的随机、开放标签、交叉研究。每位患者都进行了 2 项单独的（30 天内）稳态 12 小时药代动力学（PK）研究，使用压碎的和完整的 200/50mg 洛匹那韦/利托那韦片剂。
在给药前（0 小时）、1、2、4、6、8 和 12 小时后采集洛匹那韦和利托那韦的 PK 血样。通过高效液相色谱法测量洛匹那韦和利托那韦的血浆浓度，以计算浓度-时间曲线下面积（AUC）和清除率的非房室模型。Wilcoxon 符号秩检验比较了压碎和完整片剂的 PK 值。
12 名儿童，中位年龄 13 岁（10-16 岁），每天服用 550/138mg·m(-2)洛匹那韦/利托那韦，每 12 小时一次。压碎和完整片剂后的中位洛匹那韦 AUC 分别为 92mg·hr·L(-1)和 144mg·hr·L(-1)，AUC 比值为 0.55（P=0.003）。压碎和完整片剂的中位利托那韦 AUC 分别为 7mg·hr·L(-1)和 13.3mg·hr·L(-1)，AUC 比值为 0.53（P=0.006）。
给儿童服用压碎的 200/50mg 洛匹那韦/利托那韦片剂会显著降低洛匹那韦和利托那韦的暴露，AUC 分别减少 45%和 47%。为确保需要这种治疗的患者有足够的洛匹那韦暴露，需要增加剂量和治疗药物监测。如果可能的话，应避免使用压碎的洛匹那韦/利托那韦片剂。
