Clinical Pharmacology and Pharmacometrics, AbbVie, Inc., North Chicago, IL, USA.
Bioanalysis, AbbVie, Inc., North Chicago, IL, USA.
J Pharm Sci. 2021 Dec;110(12):3963-3968. doi: 10.1016/j.xphs.2021.08.037. Epub 2021 Sep 13.
Lopinavir/ritonavir (LPV/r-A, Kaletra®), a fixed dose, co-formulated antiviral therapy for the treatment of HIV infection has been used worldwide for over two decades. Both active substances have low solubility in water and low membrane permeability. LPV/r-A tablets contain key excipients critical to ensuring acceptable bioavailability of lopinavir and ritonavir in humans. An established dog pharmacokinetic model demonstrated several generic LPV/r tablet formulations have significant oral bioavailability variability compared to LPV/r-A.
Analytical characterizations of LPV/r-B tablets were performed and a clinical study was conducted to assess the relative bioavailability of Kalidavir® (LPV/r-B) 400/100 mg tablets relative to Kaletra® (LPV/r-A) 400/100 mg tablets under fasting conditions.
The presence of active substances were confirmed in LPV/r-B tablets in an apparent amorphous state at essentially the labeled amounts, and dissolution profiles were generally similar to LPV/r-A tablets. Excipients in the tablet formulation were found to be variable and deviate from the labeled composition. Lopinavir and ritonavir exposures (AUC) following LPV/r-B administration were approximately 90% and 20% lower compared to that of LPV/r-A.
LPV/r-B was not shown to be bioequivalent to LPV/r-A.
洛匹那韦/利托那韦（LPV/r-A，克力芝®）是一种固定剂量、复方抗病毒疗法，用于治疗人类免疫缺陷病毒（HIV）感染，已在全球使用了二十多年。两种活性物质在水中的溶解度低，膜通透性也低。LPV/r-A 片剂含有确保洛匹那韦和利托那韦在人体中可接受生物利用度的关键赋形剂。已建立的犬药代动力学模型表明，与 LPV/r-A 相比，几种通用 LPV/r 片剂配方的口服生物利用度具有显著的可变性。
对 LPV/r-B 片剂进行了分析特性表征，并进行了一项临床研究，以评估 Kalidavir®（LPV/r-B）400/100mg 片剂相对于 Kaletra®（LPV/r-A）400/100mg 片剂在禁食条件下的相对生物利用度。
在 LPV/r-B 片剂中以明显的无定形状态存在活性物质，其含量基本上与标签上的含量一致，并且溶解曲线通常与 LPV/r-A 片剂相似。片剂配方中的赋形剂被发现是可变的，与标签组成有偏差。与 LPV/r-A 相比，LPV/r-B 给药后洛匹那韦和利托那韦的暴露量（AUC）分别降低了约 90%和 20%。
LPV/r-B 与 LPV/r-A 未显示生物等效性。
