The Concentration Of Dexmedetomidine Nasal Drops In Rabbit Plasma Was Determined By Uplc-ms/MS And Its Pharmacokinetic Study

BackgroundDexmedetomidine is a new class of imidazole derivatives with good lipophilic properties.It is a long-acting alpha 2-adrenergic receptor agonist.Compared with clonidine,its affinity to the alpha 2-adrenergic receptor was 8 times higher.Dexmedetomidine is often used as a preoperative drug because of its sedative,analgesic and anti-anxiety effects.Currently,transnasal infusion of dexmedetomidine is used for sedation of preoperative anesthesia in children,which is simple and fast^[1].Dexmedetomidine is absorbed through nasal mucosa and can be used in small doses to achieve sedative effect and reduce other adverse reactions of gastrointestinal system and rapid intravenous infusion.Studies on the pharmacokinetics of intravenous administration of dexmedetomidine have been reported,but the pharmacokinetics of intravenous administration via nasal drip has not been reported in China.Based on the above studies,we planned to study the change of plasma concentration of dexmedetomidine hydrochloride absorbed through nasal mucosa in adult New Zealand white rabbits,so as to provide reference for the clinical study and application of transnasal drip of dexmedetomidine.ObjectiveThe pharmacokinetics of dexmedetomidine hydrochloride were studied following a single nasal(5?g.kg^-1 and 20?g.kg^-1)dose given to New Zealand white rabbits by using ultra performance liquid chromatography tandem mass spectrometry.MethodsThe open and parallel test design of a single nasal drop is adopted.The 12 New Zealand white rabbits were randomly divided into two doses(5?g.kg^-1 and 20?g.kg^-1),six in each group,the half is male and the other half is female.Determine the dexmede-tomidine concentration of blood drugs at different times using UPLC-MS/MS to,and phoenix win nonlin 7.0 software and SPSS for pharmacogenic parameter calculation and statistical analysis.Resultswhen the group of rabbits were intranasally administered with dexmedetomidine5?g.kg^-1,the median maximum concentration is 8.01 ng.L^-1,time to maximum concen-tration is10 min,mean elimination half-life was 111min.The other group of rabbits were intranasally administered with dexmedetomidine 20?g.kg^-1,the median maximum concen-tration is 92.8 ng.L^-1,time to maximum concentration is 6.7 min,mean elimination half-life was 68min.Conclusion1.With the increase of the concentration of dexmetomidine in nasal drops,the time to reach the peak value was shorter.The concentration of dexmetomidine in nasal drops increased,and the increase of peak concentration was more obvious.The elimination of the drug did not slow down with the change of the concentration of dexmetomidine intranasal drops.2.In the range of 5?g.kg^-11 to 20?g.kg^-1concentation,the dexmedetomidine in the white rabbit in New Zealand follow a nonlinear dynamic feature.