Bamlanivimab and etesevimab are neutralizing antibodies indicated for treatment 
of coronavirus disease 2019 (COVID-19) in patients with early mild or moderate 
disease. We present the use of pharmacokinetic/pharmacodynamic (PK/PD) modeling 
that characterizes the timecourse of viral load obtained from 2,970 patients 
from 2 phase II clinical trials. The model was used for identification of 
optimal doses that would result in at least 90% of patients achieving serum drug 
concentrations that result in 90% of maximum drug effect (IC90) for at least 
28 days. The serum IC90 (95% confidence interval) was estimated to be 4.2 
(3.2-4.3) µg/mL for bamlanivimab and 12.6 (9.7-12.8) µg/mL for etesevimab. 
Observed clinical trial data confirmed PK and PK/PD model predictions that doses 
of 700 mg bamlanivimab and 1,400 mg etesevimab would result in maximum reduction 
in viral load, with no additional effect seen at higher doses. No dose 
adjustment is recommended as age, sex, race, baseline viral load, and hepatic 
impairment did not have a significant impact on the PK of the antibodies. 
Earlier drug administration resulted in greater reductions in viral load, 
demonstrating the importance of receiving treatment as soon as possible. 
Relative to placebo, typical reduction in viral load over a 7-day period was 
estimated to be 80 or 93% (drug administered 4 days or 1 day after the onset of 
symptoms, respectively), P < 0.0001. PK/PD modeling and simulation was pivotal 
throughout the drug development and emergency use authorization process.