Factors influencing Nirmatrelvir/Ritonavir concentration in patients with COVID-19

Background In the filed of antiviral therapy, effective therapeutic concentration is beneficial to shorten the recovery time of patients and reduce the transmission rate.The aim of this study is to retrospectively analyze the factors that lead to the drug concentration of Nirmatrelvir /Ritonavir (NMV/RTV) not reaching the standard. Methods In this study, the NMV/RTV drug concentration(Cnmv/rtv) data (n = 114) of COVID-19 patients over 18 years old were collected from May 2022 to July 2022, and the results of the patients were retrospectively compared. According to the analysis of the early study of NMV/RTV, combined with the research results at home and abroad, according to whether the measured drug concentration > 987 ng/ml, the patients were divided into target group and non-target group,The non-target group was defined as not reaching the trough concentration level. Results Serum NMV/RTV concentration in adult patients was correlated with prognostic nutritional index [PNI, (P < 0.05)], height (P < 0.05), weight (P < 0.05) and creatinine clearance [Crcl, (P < 0.05)]. Multivariate analysis showed that height, weight, PNI, lymphocyte (LYM) and CrCl were independent influencing factors of NMV/RTV trough concentration. However, after the correction of BMI calculation, there was no correlation between NMV/RTV and BMI, so in the clinical medication plan, the drug was not adjusted according to the height and weight. Conclusions The serum NMV/RTV concentration of adult patients gradually decreased with the increase of CrCl. For patients with high and low CrCl, the trough concentration of NMV/RTV should be continuously monitored and the dosing regimen should be adjusted to achieve the target trough concentration in these patients to reduce the effect of CrCl. PNI is also a key factor affecting drug concentration. For poor nutritional status, drug concentration should be closely monitored and the dose should be adjusted.