Work

Analysis of Nirmatrelvir Entry into Pulmonary Lining Fluid in Patients with COVID‐19: A Unique Perspective to Explore and Understand the Target Plasma Concentration of 292 ng/mL in Antiviral Activity

Year: 2024

Type: article

Abstract: BACKGROUND: value (181 nM). However, the current exposure-effect relationships (ER) analysis of viral load in patients enrolled in the EPIC-HR study has not revealed clinically significant trends in the ER. Given that the lungs are the primary site of COVID-19 infection, we aim to further understand this exposure relationship by exploring and analyzing the penetration characteristics of nirmatrelvir in the lungs. OBJECTIVES: To explore and understand the target plasma concentration of 292 ng/mL in antiviral activity. METHODS: We identified all critically ill patients with coronavirus disease 2019 who received nirmatrelvir/ritonavir treatment in the respiratory intensive care unit of Changhai hospital between January 2023 and October 2023. Samples of plasma and bronchoalveolar lavage fluid were obtained at pre-dose trough concentrations after administration of nirmatrelvir (NMV). The relationship between NMV levels in plasma and the epithelial lining fluid (ELF) was assessed by determining concentrations of NMV. RESULTS: There was a significant relationship between NMV levels in plasma and ELF (ELF = 0.4976*PLASMA- 204; R = 0.96), with a correlation whose slope (0.4976) suggested that the blood-to-ELF ratio of drug penetration was 2:1. A negative value from the equation indicates that NMV requires to reach baseline concentration to penetrate the ELF. CONCLUSIONS: The relationship between NMV levels in plasma and ELF with low permeability and a negative baseline value suggests that the target plasma concentration of 292 ng/mL is insufficient for antiviral activity. This study provides a unique perspective to explore and understand no clinically meaningful trend of exposure-response relationships in patients enrolled in EPIC-HR.

Source: Immunity Inflammation and Disease

DOI: 10.1002/iid3.70075

Authors: Wenjing Zhang, Lin Xia, Zhilong Yuan, Yang Jiao, Zhuo Wang

Institutions: Changhai Hospital, Bengbu Medical College

Language: English

Topic: COVID-19 Clinical Research Studies

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,240