A Model of Acetaminophen Pharmacokinetics and its Effect on Continuous Glucose Monitoring Sensor Measurements

Some of commercial continuous glucose monitoring (CGM) devices, i.e., minimally-invasive sensors able to measure almost continuously glucose concentration in the subcutaneous tissue, recently received the regulatory approval to be used for making therapeutic decisions in diabetes management. A fundamental requirement for its safe and effective use is represented by the accuracy of CGM measurements. However, despite recent advances in sensors accuracy and reliability, CGM still suffers from inaccuracy problems in presence of pharmacologic interferences, e.g., the common orally administered acetaminophen (APAP), which artificially raises CGM glucose readings for several hours. A model of the artifact induced by APAP on CGM measurements would be useful to design algorithms to compensate such a distortion. The aim of this work is to exploit the data published by previous literature studies to design a model of oral APAP pharmacokinetics and its effect on glucose concentration measured by CGM sensors. Specifically, the developed model was identified on average data of both plasma APAP concentration and the APAP effect on CGM profiles after an oral administration of 1000 mg of APAP. The APAP effect on CGM readings was estimated from the difference observed, in the same study, between the glucose profile measured by a Dexcom G4 Platinum sensor and the plasma glucose concentration. The model was validated by comparing the simulated effect of mealtime APAP administration in CGM measurements of 100 virtual subjects generated by the UVA/Padova Type 1 Diabetes (TID) Simulator vs. the effect observed in a clinical study by Maahs et al. (Diabetes Care, 2015) in 40 TID subjects taking APAP at breakfast. Results suggest that the proposed model is able to reliably describe the mean APAP effect on CGM measurements.