An important consideration in alcohol pharmacokinetic modeling arises from what, where, when, and in what context to measure alcohol or alcohol metabolites after administration. The brain alcohol exposure time course is one common outcome of interest, as that trajectory is a key contributor to intoxication. Unfortunately, it is generally difficult to directly measure human brain alcohol concentration. However, as a low-volume but high blood flow organ, brain alcohol concentration closely follows arterial concentration (shown in human participants with MRS, (163)). Noteworthy, as described above, there are significant time-varying arterio-venous differences in BAC (99), but the sampling of arterial, in contrast to venous blood, is challenging and poses an increased risk to study participants. Fortunately, end-expiratory breath alcohol concentration closely follows arterial blood alcohol concentration (see (100) as an example), leading to the use of the breathalyzer as a practical measure to predict brain alcohol concentration.
