Dexmedetomidine Clearance Decreases with Increasing Drug Exposure: Implications for Current Dosing Regimens and Target-controlled Infusion Models Assuming Linear Pharmacokinetics

ConclusionsThis study developed a nonlinear three-compartment pharmacokinetic model that accurately described dexmedetomidine plasma concentrations. Dexmedetomidine may be safely administered up to target-controlled infusion targets under 2  ng · ml–1 using the Hannivoort model, which assumed linear pharmacokinetics. Consideration should be taken during long-term administration and during an initial loading dose when following the dosing strategies of the current guidelines.Editor ’s PerspectiveWhat We Already Know about This TopicDexmedetomidine pharmacokinetic models underpredict the measured plasma target-controlled infusion concentrations that are higher than those used in the model validation studiesThe elimination clearance of high hepatic extraction ratio drugs like dexmedetomidine is determined by liver blood flow and not enzyme activityWhat This Article Tells Us That Is NewThe data of 48 subjects from two published pharmacokinetic studies were pooled to build a three-compartment pharmacokinetic model with nonlinear elimination clearance that successfully predicted plasma dexmedetomidine concentrations over a wide concentration rangeCardiac output did not explain between-subject or within-subject variability in dexmedetomidine elimination clearanceDexmedetomidine elimination clearance may decrease with increasing plasma concentrations because it alters the liver blood flow –to–cardiac output ratio in a concentration-dependent manner

Source: Anesthesiology - January 16, 2022 Category: Anesthesiology Source Type: research