A phrase we often hear among pharmacometricians is “let the data speak.” This is often good advice, but sometimes data are really bad at speaking, and letting them do so can create more questions than answers, particularly when the questions are complex.

With pharmacokinetic modeling, stationarity is typically assumed (i.e., volumes and clearances do not vary for the duration of the study). In this issue of Anesthesiology, Alvarez-Jimenez et al. report data indicating that this assumption has most likely been violated for dexmedetomidine elimination clearance and suggest, in their title, that this finding has implications for dexmedetomidine dosing. We will therefore discuss three possible sources of this nonstationarity. As always, context is important, so for our considerations, the drug is assumed to be administered by intravenous infusion (dosing) either at a fixed rate or a variable rate (e.g., target-controlled infusion). During infusion, plasma...

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