Some cannabinoid exposure estimates extended beyond observed sampling using an uncertain terminal fit. Area under the curve to the last measurement and area extrapolated to infinity should remain separate.
The authors identified the limitation
In the THC/CBD interaction experiment, the elimination rate constant was estimated over less than two half-lives for most CBD and 11-hydroxy-THC profiles. Several fitted profiles had low regression precision. For several CBD profiles, the extrapolated portion of total area under the curve exceeded 20%.
Those limitations concern the tail of the estimated concentration-time curve. They do not mean that every measured plasma concentration or observed peak was invented.
Observed and extrapolated exposure answer related questions
Area to the final quantifiable sample uses the observed collection window. Area to infinity adds a modeled terminal component. If the terminal slope is poorly characterized, the added component can be uncertain even when earlier samples are informative. A half-life estimate also inherits uncertainty from that slope.
What to retain in an opinion
Specify which exposure metric supports an interaction claim and whether its calculation relied heavily on extrapolation. Do not use a fitted terminal parameter as a precise clock for one person’s last dose. The small healthy-volunteer experiment measured pharmacokinetics, leaving the relationship between those tail estimates and actual functional impairment untested.
Related reading: interpreting proposed CBD mechanisms.
Research cited
Stott and colleagues (2013). A Phase I, open-label, randomized, crossover study in three parallel groups to evaluate the effect of Rifampicin, Ketoconazole, and Omeprazole on the pharmacokinetics of THC/CBD oromucosal spray in healthy volunteers. DOI: 10.1186/2193-1801-2-236.
Leave a Reply