Pharmacokinetic and pharmacodynamic evaluation study of etomidate: a randomized, open-label, 2-period crossover study in healthy Chinese subjects.

Etomidate is a sedative and hypnotic drug through intravenous administration that act on the central nervous system through GABA (Gamma-Amino Butyric Acid) receptors, which is widely used in anesthesia induction and maintenance and long-term sedation in severe patients. The study aimed to evaluate the pharmacokinetic and pharmacodynamic properties of two etomidate fat emulsions after administration through the intravenous infusion pump in healthy Chinese subjects. A randomized, open-label, 2-period crossover study was performed in 52 healthy subjects. The wash-out period was 7 days. Blood samples and pharmacodynamic index values were collected at the specified time points. Etomidate concentrations were measured using validated liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were analyzed using a non-compartment model method. Pharmacodynamic parameters were calculated using pharmacodynamic index values. The study also evaluated the safety of the etomidate. Both the pharmacokinetic parameters and pharmacodynamic parameters result of the test and reference formulation were very similar. The 90% confidence intervals (CI) of the geometric least-squares mean (GLSM) ratios of the test to reference formulation were 91.33-104.96% for the maximum plasma concentration (Cmax), 97.21-102.03% for the area under the plasma concentration time curve from time 0 to the time of the last measurable concentration (AUC0-t), and 97.22-102.33% for the area under the plasma concentration time curve from time 0 to infinity (AUC0-∞). Meanwhile, the 90% CI of the GLSM ratios of the test to reference formulation were 102.28-110.69% for the minimal BIS value (BISmin), 99.23-101.17% for the area under the BIS time curve from time 0-60 min after administration (BISAUC0-60 min), respectively. The 90% CI of these pharmacokinetic and pharmacodynamic parameters all fall in the accepted bioequivalence range of 80.00-125.00%. No serious adverse events occurred during the study. This study has shown that the etomidate fat emulsion test and reference formulation had similar pharmacokinetic and pharmacodynamic characteristics in vivo. The two formulations exhibited good safety and well-tolerance.Clinical trials registration number: http://www.chinadrugtrials.org.cn/index.html . # CTR20191836.

Efeitos hemodinâmicos do etomidato, midazolam e tiopental: estudo em induçao no homem e em coraçao perfundido de ratos / Hemodynamic effects of etomidate, midazolam and thiopental during induction in man and on the isolated heart of rats

Os autores visaram comparar os efeitos no sistema cardiovascular, o tempo de induçao anestésica e possíveis efeitos colaterais do etomidato, midazolam e tiopental sódico, todos usados como hipnóticos e indutores da anestesia geral. Para tal, o presente trabalho foi dividido em duas etapas: uma clínica e outra laboratorial. Na primeira etapa, utilizaram-se 30 pacientes, distribuídos em três grupos de 10, que haviam recebido fentanil (0,1 mg) e atropina (0,5 mg) por via venosa, como medicaçao pré-anestésica e aos quais administraram-se, respectivamente, etomidato (0,3 mg.kgúû), midazolam (0,3 mg.kgúû) e tiopental sódico (4 mg.kgúû). Os parâmetros avaliados nesses pacientes foram a frequência cardíaca, a pressao arterial sistólica e diastólica, o tempo de induçao anestésica e a ocorrência de mioclinias, dor à injeçao e flebites. O grupo do etomidato mostrou uma maior estabilidade cardiocirculatória quando comparado com os demais grupos. Porém, houve taquicardia e ligeira elevaçao da pressao arterial no momento correspondente à intubaçao traqueal. Esse fato foi de maior intensidade com o midazolam. Na etapa laboratorial, procurou-se evidenciar os efeitos dessas três drogas no coraçao isolado e perfundido de ratos, utilizando para tal 30 animais. Pela análise estatística dos dados obtidos na preparaçao in vitro, ficou evidenciada bradicardia significativa para os três fármacos, embora com o tiopental sódico essa resposta tenha sido mais pronunciada após o uso de doses mais elevadas do barbitúrico. Os três fármacos estudados desenvolveram açao depressora da atividade miocárdica, dose-dependente