Regional Center of Pharmacovigilance, Pharmacology Department, Cochin Hospital, AP-HP Centre-Université de Paris.
Pharmacology Department, Cochin Hospital, AP-HP Centre-Université de Paris.
Ther Drug Monit. 2021 Feb 1;43(1):131-135. doi: 10.1097/FTD.0000000000000838.
Although the efficacy of lopinavir/ritonavir has not been proven, it has been proposed as an off-label treatment for COVID-19. Previously, it has been reported that the plasma concentrations of lopinavir significantly increase in inflammatory settings. As COVID-19 may be associated with major inflammation, assessing the plasma concentrations and safety of lopinavir in COVID-19 patients is essential.
Real-world COVID-19 data based on a retrospective study.
Among the 31 COVID-19 patients treated with lopinavir/ritonavir between March 18, 2020 and April 1, 2020, higher lopinavir plasma concentrations were observed, which increased by 4.6-fold (interquartile range: 3.6-6.2), compared with the average plasma concentrations in HIV. Lopinavir concentrations in all except one patient were above the upper limit of the concentration range of HIV treatment. Approximately one to 5 patients prematurely stopped treatment mainly because of an ADR related to hepatic or gastrointestinal disorders.
Lopinavir plasma concentrations in patients with moderate-to-severe COVID-19 were higher than expected, and they were associated with the occurrence of hepatic or gastrointestinal adverse drug reactions. However, a high plasma concentration may be required for in vivo antiviral activity against SARS-CoV-2, as suggested by previous studies. Therefore, in the absence of adverse drug reaction, lopinavir dosage should not be reduced. Caution is essential because off-label use can be associated with a new drug safety profile.
洛匹那韦/利托那韦虽然尚未被证明有效，但已被提议作为 COVID-19 的超适应证治疗药物。此前有报道称，洛匹那韦在炎症环境中的血浆浓度显著升高。由于 COVID-19 可能与严重炎症有关，因此评估 COVID-19 患者中洛匹那韦的血浆浓度和安全性至关重要。
基于回顾性研究的真实世界 COVID-19 数据。
在 2020 年 3 月 18 日至 4 月 1 日期间接受洛匹那韦/利托那韦治疗的 31 例 COVID-19 患者中，观察到更高的洛匹那韦血浆浓度，与 HIV 的平均血浆浓度相比，增加了 4.6 倍（四分位距：3.6-6.2）。除 1 例患者外，所有患者的洛匹那韦浓度均高于 HIV 治疗浓度范围的上限。大约有 1 至 5 例患者因与肝或胃肠道紊乱相关的不良反应而提前停止治疗。
中重度 COVID-19 患者的洛匹那韦血浆浓度高于预期，与肝或胃肠道不良药物反应的发生有关。然而，如先前研究所示，高血浆浓度可能是针对 SARS-CoV-2 的体内抗病毒活性所必需的。因此，在没有不良反应的情况下，不应减少洛匹那韦的剂量。由于超适应证使用可能会带来新的药物安全性特征，因此需要谨慎。
