Clinical Pharmacy, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
J Antimicrob Chemother. 2010 Mar;65(3):538-42. doi: 10.1093/jac/dkp472. Epub 2010 Jan 7.
To determine the pharmacokinetic profiles of lopinavir and ritonavir in two newly developed generic co-formulations for HIV-infected children (Lopimune paediatric tablets and granules, 100/25 mg of lopinavir/ritonavir, Cipla Pharmaceuticals), and to compare these with the branded product (Kaletra).
This Phase I, comparative, open-label, three-period, single-dose, crossover study was designed as a pilot study to exclude large (>40%) differences in the exposure to lopinavir. Single doses of medication, normalized to 400 mg of lopinavir, were administered on an empty stomach, 1 week apart. A 32 h pharmacokinetic curve was recorded. In an additional part of the study, in five of the same volunteers, a pharmacokinetic curve was recorded after administration of the Lopimune granules and Kaletra oral solution, both with food.
Twelve healthy subjects were enrolled (four females). The median (range) age, height and body weight were 24 (21-55) years, 1.79 (1.63-1.95) m and 72 (51-87) kg, respectively. The median [interquartile range (IQR)] AUC(0-t) of lopinavir was 71.8 (48.8-93.5), 38.7 (28.7-52.2) and 58.7 (42.5-79.4) mg.h/L with Kaletra tablets, Lopimune granules and Lopimune paediatric tablets, all taken on an empty stomach, respectively. The respective C(max) values were 7.2 (5.8-8.3), 4.6 (4.1-5.2) and 6.5 (5.0-7.1) mg/L after intake of the different formulations. When comparing the Lopimune formulations with the reference product Kaletra, for all parameters the differences were statistically significant (P <or= 0.015). Ritonavir exposure was also lower after intake of the generic formulations versus Kaletra. When the five subjects took the Lopimune granules or Kaletra solution with food, the median (IQR) AUC(0-t) of lopinavir was 58.5 (55.4-77.6) and 49.6 (39.1-58.1) mg.h/L, respectively.
Large differences in pharmacokinetic parameters can be excluded for Lopimune paediatric tablets when compared with the branded product and taken on an empty stomach, and also for Lopimune granules when these are taken with food.
确定两种新开发的用于治疗感染 HIV 的儿童的洛匹那韦利托那韦通用复方制剂（Lopimune 儿科片剂和颗粒剂，100/25 毫克洛匹那韦/利托那韦，西普拉制药公司）的药代动力学特征，并将其与品牌药物（克力芝）进行比较。
这是一项 I 期、比较、开放标签、三周期、单剂量、交叉研究，旨在作为排除洛匹那韦暴露量出现较大（>40%）差异的初步研究。空腹单剂量用药，归一化为 400 毫克洛匹那韦，间隔 1 周。记录 32 小时的药代动力学曲线。在研究的另一部分，在相同的 5 名志愿者中，在给予 Lopimune 颗粒和克力芝口服液后，均在进食时记录药代动力学曲线。
共纳入 12 名健康受试者（4 名女性）。中位（范围）年龄、身高和体重分别为 24（21-55）岁、1.79（1.63-1.95）m 和 72（51-87）kg。空腹服用克力芝片剂、Lopimune 颗粒和 Lopimune 儿科片剂时，洛匹那韦的 AUC（0-t）中位数（四分位距（IQR））分别为 71.8（48.8-93.5）、38.7（28.7-52.2）和 58.7（42.5-79.4）mg·h/L。相应的 C（max）值分别为 7.2（5.8-8.3）、4.6（4.1-5.2）和 6.5（5.0-7.1）mg/L。与参比药物克力芝相比，所有参数的差异均具有统计学意义（P<0.015）。与克力芝相比，服用通用制剂后利托那韦的暴露量也较低。当 5 名受试者服用 Lopimune 颗粒或克力芝口服液时，洛匹那韦的 AUC（0-t）中位数（IQR）分别为 58.5（55.4-77.6）和 49.6（39.1-58.1）mg·h/L。
与参比药物相比，空腹服用 Lopimune 儿科片剂时，洛匹那韦的药代动力学参数差异较大，而与品牌药物相比，服用 Lopimune 颗粒剂时，当与食物一起服用时，洛匹那韦的药代动力学参数差异较大。
