Therapeutic Drug Monitoring of Nirmatrelvir/Ritonavir (Paxlovid) in Patients Treated for COVID-19: Results From a Prospective Multicenter Observational Study.

BACKGROUND

Paxlovid is a combination of the antiviral agents nirmatrelvir and ritonavir indicated for the oral treatment of high-risk, symptomatic patients with coronavirus disease 2019 (COVID-19). As real-world data on the plasma concentrations of nirmatrelvir/ritonavir (Paxlovid) are limited, the aim of this study was to investigate nirmatrelvir/ritonavir plasma trough levels in a clinical setting using therapeutic drug monitoring.

METHODS

A prospective, noninterventional, multicenter, observational clinical study was conducted in which the plasma trough levels of nirmatrelvir/ritonavir were simultaneously determined by using liquid chromatography tandem mass spectrometry in patients with symptomatic COVID-19. The blood samples were collected on days 1, 3, and 5 after the first full-dose day (day 0), and patient data such as sex, height, weight, renal function, liver enzymes, and concomitant (co-) medications were obtained to describe the plasma levels with respect to potential influencing factors.

RESULTS

A total of 46 blood samples from 21 patients were analyzed. The geometric mean C min was 4997 ng/mL for nirmatrelvir and 529.4 ng/mL for ritonavir. The plasma concentrations covered a wide range, the highest being observed in patients with advanced age and renally excreted comedications. Patients older than 65 years had a significantly higher risk of achieving excessive plasma trough concentrations above 8840 ng/mL for nirmatrelvir and 1440 ng/mL for ritonavir compared with younger patients (odds ratio 11.2, 95% confidence interval 1.04-120.4).

CONCLUSIONS

The plasma trough concentrations of nirmatrelvir and ritonavir in patients treated for symptomatic COVID-19 were higher than the reference values of 2210 ng/mL for nirmatrelvir and 360 ng/mL for ritonavir stated in the product characteristics. Advanced age and renally eliminated comedication were identified as possible influencing factors that warrant further investigation.