洛比那韦
洛比那韦/利托那韦
生物利用度
利托那韦
生物等效性
药代动力学
药理学
化学
色谱法
医学
人类免疫缺陷病毒(HIV)
病毒载量
病毒学
抗逆转录病毒疗法
作者
Ahmed Mahdi Saeed,Jeffery M. Schmidt,Wijith Munasinghe,Bhadrish K. Vallabh,Michael F. Jarvis,John B. Morris,Nael M. Mostafa
标识
DOI:10.1016/j.xphs.2021.08.037
摘要
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.
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