van der Lugt Jasper, Lange Joep, Avihingsanon Anchalee, Ananworanich Jintanat, Sealoo Siriporn, Burger David, Gorowara Meena, Phanuphak Praphan, Ruxrungtham Kiat
The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Thai Red Cross AIDS Research Centre (TRCARC), Bangkok, Thailand.
Antivir Ther. 2009;14(7):1001-4. doi: 10.3851/IMP1410.
Generic drugs can contribute to access to treatment for HIV-infected patients. However quality and safety remains an issue of concern. Therefore, we evaluated minimal plasma concentrations and short-term safety of a generic lopinavir/ritonavir 200/50 mg tablet formulation.
In a single-centre prospective pilot study, patients receiving protease-inhibitor-based antiretroviral treatment were switched to a generic lopinavir/ritonavir tablet at the standard dose (400/100 mg twice daily). Minimum drug concentrations (C(min)) of lopinavir and ritonavir were performed before switching (in 16 patients who were on Kaletra((R)) soft-gel capsules) and after 4 weeks (in all patients). Plasma levels of lopinavir and ritonavir were determined by a validated HPLC method. Either the Wilcoxon signed-rank or Mann-Whitney U test was used to compare the groups.
A total of 37 patients (18 females) were included in the study. Two stopped their study medications prematurely because of intolerance. The median (interquartile range) lopinavir C(min) was 7.2 mg/l (5.8-8.3) and no patients had subtherapeutic levels <1.0 mg/l. No significant difference of lopinavir C(min) levels was found between Kaletra((R)), and the generic product (P=0.224). By contrast, the C(min) of generic ritonavir was higher (P=0.012). Food did not affect the drug levels. Mild gastrointestinal complaints were reported in 12 patients.
The generic lopinavir/ritonavir tablet showed C(min) plasma concentrations similar to what is described for the branded product, with good stability, independent of food intake. These data support the efforts in scaling up access to generic second-line treatment in middle- and low-income countries.
仿制药有助于艾滋病毒感染患者获得治疗。然而，质量和安全性仍是一个令人担忧的问题。因此，我们评估了一种洛匹那韦/利托那韦200/50毫克仿制药片制剂的最低血浆浓度和短期安全性。
在一项单中心前瞻性试点研究中，接受基于蛋白酶抑制剂的抗逆转录病毒治疗的患者被换用标准剂量（每日两次，每次400/100毫克）的洛匹那韦/利托那韦仿制药片。在换药前（16名服用克力芝（R）软胶囊的患者）和4周后（所有患者）检测洛匹那韦和利托那韦的最低药物浓度（C(min)）。采用经过验证的高效液相色谱法测定洛匹那韦和利托那韦的血浆水平。使用Wilcoxon符号秩检验或Mann-Whitney U检验对各组进行比较。
共有37名患者（18名女性）纳入研究。两名患者因不耐受而提前停止研究用药。洛匹那韦C(min)的中位数（四分位间距）为7.2毫克/升（5.8 - 8.3），没有患者的治疗水平低于1.0毫克/升。克力芝（R）与仿制药之间的洛匹那韦C(min)水平无显著差异（P = 0.224）。相比之下，仿制药利托那韦的C(min)更高（P = 0.012）。食物不影响药物水平。12名患者报告有轻度胃肠道不适。
洛匹那韦/利托那韦仿制药片的C(min)血浆浓度与品牌产品相似，稳定性良好，与食物摄入无关。这些数据支持在中低收入国家扩大仿制药二线治疗可及性的努力。
