A nonlinear pharmacokinetic model used in calibrating a transdermal alcohol transport concentration biosensor data analysis software

2014-08-06In Rosen's earlier work [1] [4], blood (BAC) or breath (BrAC) alcohol concentration was estimated from biosensor measurements of transdermal alcohol concentration (TAC) by forward distributed parameter models, which need to be calibrated by alcohol challenge data. The alcohol challenge data was collected from a TAC biosensor and a breath analyzer after giving patient who was wearing with a TAC biosensor a measured dose of alcohol and blowing into a breath analyzer. This process is required for each patient before the device was used to estimate BrAC from field TAC. In this research, we used a pharmacokinetic metabolic absorption/elimination model and drinking diary to estimate the BrAC or BAC, and then we used the estimated BrAC or BAC and TAC data of first episode as the alcohol challenge data to calibrate forward distributed parameter model for transdermal transport of ethanol. The pharmacokinetic model can be determined by solving a nonlinear least squares problem using adjoint based gradient computation. We compared the parameters of the forward model obtained using BrAC from alcohol challenges with that obtained using estimated BrAC from our pharmacokinetic model and drinking diary. We assessed the efficacy of our calibration approach by comparing the performances of forward models with two groups of parameters generated by original calibration approach and our approach. Finally, we calibrated the transdermal alcohol transport model using the pharmacokinetic model with both population parameters and per‐patient parameters and computed peak BrAC, time of peak BrAC and area under the BrAC curve in two cases