The majority of penicillin allergy labels are incorrect and a label of penicillin allergy is associated with worse outcomes and increased use of healthcare services. Penicillin allergy assessment and de-labeling may be considered in critically ill patients. An oral penicillin challenge is a common component of most penicillin allergy protocols. In critical illness, the enteral route may not be an option and is less reliable due to altered absorption kinetics. In this study, simulations were undertaken to determine an intravenous infusion dosing schedule for critically ill patients that matches the concentration-time profile of an oral penicillin drug provocation test in the general population. These simulations may help clinicians develop guidelines for intravenous infusion penicillin drug provocation tests for critically ill patients.