Abstract

Background

The combination lopinavir/ritonavir is recommended to treat HIV-infected patients at the dose regimen of 400/100 mg q12h, oral route. The usual lopinavir trough plasma concentrations are 3000–8000 ng/mL. A trend towards a 28 day mortality reduction was observed in COVID-19-infected patients treated with lopinavir/ritonavir.

Objectives

To assess the plasma concentrations of lopinavir and ritonavir in patients with severe COVID-19 infection and receiving lopinavir/ritonavir.

Patients and methods

Mechanically ventilated patients with COVID-19 infection included in the French COVID-19 cohort and treated with lopinavir/ritonavir were included. Lopinavir/ritonavir combination was administered using the usual adult HIV dose regimen (400/100 mg q12h, oral solution through a nasogastric tube). A half-dose reduction to 400/100 mg q24h was proposed if lopinavir C_trough was >8000 ng/mL, the upper limit considered as toxic and reported in HIV-infected patients. Lopinavir and ritonavir pharmacokinetic parameters were determined after an intensive pharmacokinetic analysis. Biological markers of inflammation and liver/kidney function were monitored.

Results

Plasma concentrations of lopinavir and ritonavir were first assessed in eight patients treated with lopinavir/ritonavir. Median (IQR) lopinavir C_trough reached 27 908 ng/mL (15 928–32 627). After the dose reduction to 400/100 mg q24h, lopinavir/ritonavir pharmacokinetic parameters were assessed in nine patients. Lopinavir C_trough decreased to 22 974 ng/mL (21 394–32 735).

Conclusions

In mechanically ventilated patients with severe COVID-19 infections, the oral administration of lopinavir/ritonavir elicited plasma exposure of lopinavir more than 6-fold the upper usual expected range. However, it remains difficult to safely recommend its dose reduction without compromising the benefit of the antiviral strategy, and careful pharmacokinetic and toxicity monitoring are needed.

中文翻译：

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三个猪大肠杆菌的分离鉴定共同携带tet（X4）和cfr。

摘要

背景

建议将洛匹那韦/利托那韦联合使用，以400/100 mg q12h的口服剂量方案治疗感染HIV的患者。通常的洛匹那韦波谷血浆浓度为3000–8000 ng / mL。在使用洛匹那韦/利托那韦治疗的被COVID-19感染的患者中观察到了28天死亡率降低的趋势。

目标

评估患有严重COVID-19感染并接受lopinavir / ritonavir的患者中lopinavir和ritonavir的血浆浓度。

患者和方法

纳入法国COVID-19队列中并使用lopinavir / ritonavir治疗的COVID-19感染的机械通气患者。使用通常的成人HIV剂量方案（400/100 mg q12h，通过鼻胃管口服溶液）给予洛匹那韦/利托那韦联合治疗。如果洛匹那韦C_谷浓度> 8000 ng / mL，建议在24小时内将半剂量减少至400/100 mg ，该上限被认为是有毒的，并在感染HIV的患者中报告。经过深入的药代动力学分析后确定了洛匹那韦和利托那韦的药代动力学参数。监测炎症和肝/肾功能的生物学指标。

结果

首先评估了洛匹那韦/利托那韦治疗的八名患者的洛匹那韦和利托那韦的血浆浓度。中位（IQR）洛匹那韦C_谷达到27908 ng / mL（15928–32627）。在剂量减少至400/100 mg每24小时后，对9名患者评估了lopinavir / ritonavir的药代动力学参数。罗匹那韦C_谷降至22974 ng / mL（21 394–32 735）。

结论

在有严重COVID-19感染的机械通气患者中，洛匹那韦/利托那韦的口服给药引起洛匹那韦的血浆暴露超过通常预期范围的6倍。但是，仍然很难安全地推荐降低剂量而不损害抗病毒策略的益处，并且需要仔细的药代动力学和毒性监测。