Population pharmacokinetics and pharmacodynamics of nirmatrelvir in Chinese patients with COVID-19

Abstract

Background

The pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of nirmatrelvir (NMV) are unknown in Chinese patients with COVID-19.

Objectives

To understand the PK, as well as PK–PD characteristics of NMV for optimizing the dose in Chinese patients with COVID-19.

Methods

We enrolled 141 participants who received NMV 300 mg/ritonavir (RTV) 100 mg b.i.d. for 5 days. The NMV concentrations were analyzed using 251 blood samples. PK/PD of NMV was investigated in these COVID-19 patients using a nonlinear mixed-effects model.

Results

The patients had a mean age of 82 years (range, 34–97). The absorption rate constant and apparent clearance of NMV in this Chinese cohort were 0.253 h⁻¹ and 6.83 L/h, respectively, similar to Caucasian patients. No covariates affected NMV clearance. Predicted peak (C_max) and trough concentration (C_min) under 300 mg NMV/100 mg RTV b.i.d. were 4004 and 1498 ng/mL, respectively. Although higher AUC and C_min were weakly associated with a slight increase in the number of cycle threshold (CT) of viral genes, no significant correlation was found, indicating a weak relationship between drug exposure and efficacy (CT).

Conclusions

In all, our findings suggest no ethnic PK differences, a weak and clinically insignificant relationship between drug exposure and efficacy, suitable dosage for Chinese patients (including the elderly) based on PK parameters, and the need for further studies to determine optimal regimens for high-risk patients due to inter-individual variability.