Argument for the pharmacokinetically-informed preclinical researcher: A commentary for Alcohol.

The purpose of this commentary is to advocate for the importance of carefully considering ethanol pharmacokinetics when conducting preclinical studies involving alcohol consumption. Researchers working in this field commonly use alcohol drinking as a principle or ancillary measurement. However, the amount of alcohol consumed cannot substitute for an understanding of dose, which is an essential referent in any study involving pharmacology, especially in studies using 24-h, two-bottle choice access to alcohol. Dose is the critical variable for understanding potency and efficacy, for translating both across species (including to humans) and for accurately building on preclinical work using in vitro methodologies. Nonetheless, there is a wide variety of practices when it comes to consideration of the pharmacological relevance of alcohol intake measures. Notably, there are numerous published studies reporting intake rates for which blood ethanol concentrations (BECs) would either be zero or negligible, or would be so high as to be physiologically impossible. To combat these issues, the gold standard for understanding dose should be measurement of BEC. Where this is impractical or impossible, researchers must at a minimum carefully analyze rates of alcohol intake in their population against well-understood and easily modeled pharmacokinetic factors, such as rate of intake as it compares to rate of metabolism. Similar methods are increasingly apparent in clinical studies that use pharmacological modeling (so-called "eBAC") along with measuring the rate of alcohol intake to estimate human BECs. In short, to make useful contributions to the study of alcohol drinking, authors should ensure that they are pharmacokinetically informed.