Pharmacokinetics of Lopinavir/Ritonavir Crushed Versus Whole Tablets in Children
Pharmacokinetics of Lopinavir/Ritonavir Crushed Versus Whole Tablets in Children
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DOI：
10.1097/qai.0b013e318232b057
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发表时间：
2011-12-01
影响因子：
3.6
通讯作者：
Rakhmanina, Natella
中科院分区：
文献类型：
--
作者：
Best, Brookie M.;Capparelli, Edmund V.;Rakhmanina, Natella
目的：洛匹那韦/利托那韦（Kaletra）是治疗儿童HIV感染的一线药物。在临床实践中，Kaletra片剂偶尔会被压碎用于儿科给药。本研究比较了洛匹那韦/利托那韦暴露之间的整体和粉碎片剂在HIV infected children.Design：这是一个随机的，开放标签，交叉研究的儿科患者服用洛匹那韦/利托那韦作为他们的抗逆转录病毒治疗方案的一部分。每个受试者有2个单独的（30天内）稳态12小时的药代动力学（PK）研究与粉碎和整个200/50 mg洛匹那韦/利托那韦tables.Methods：PK血样在0（给药前），1，2，4，6，8，和12小时后剂量。使用通过高效液相色谱法测量的洛匹那韦和利托那韦血浆浓度计算浓度-时间曲线下非房室面积（AUC）和清除率。Wilcoxon符号秩检验比较了压碎片剂和整片片剂之间的PK值。结果：12名儿童，中位年龄为13岁（10-16岁），每天服用550/138 mg.m（-2）洛匹那韦/利托那韦，每12小时服用一次。压碎片剂和整片片剂后的中位洛匹那韦AUC分别为92 mg.hr.L-1和144 mg.hr.L-1，AUC比为0.55（P = 0.003）。中位利托那韦AUC的粉碎和整个片剂分别为7 mg.hr.L-1和13.3 mg.hr.L-1，AUC比为0.53（P = 0.006）.结论：管理粉碎200/50 mg洛匹那韦/利托那韦片剂的儿童显着降低洛匹那韦和利托那韦的暴露，AUC分别下降了45%和47%。使用粉碎片剂需要更高的剂量和治疗药物监测，以确保需要这种做法的患者有足够的洛匹那韦暴露。如果可能，应避免使用压碎的洛匹那韦/利托那韦片剂。
Objective: 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.Design: 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.Methods: 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.Results: 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).Conclusions: 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.