| Atipamezole was a a2-adrenoceptor antagonist with an imidazole structure, and could be rapidly absorbed and distributed from the periphery to the central nervous. Atipamezole rapidly reversed sedation/anesthesia induced by α2-adrenoceptor agonists. Atipamezole had been approved used in veterinary medicine, but was not licensed for use in some animals, such as cats, in the United States.There were few reports about it in China until now. This study established a method using HPLC-FL to determine the concentration of atipamezole in plasma by taking atipamezole and specificity antagonist for miniature pigs’combined anaesthetic as subjects, and anaesthetised miniature pigs by XFM as experimental animals. This method was used as qualitative and quantitive means for studying the pharmacokinetic characteristics of atipamezole in plasma which are in Group atipamezole and Group specificity antagonist for miniature pigs’combined anaesthetic combination in miniature pigs’plasma respectively. The influence on the pharmacokinetic of atipamezole was discussed after atipamezole, flumazenil and naloxone were administrated in combination, and the antagonistic effects of atipamezole and specificity antagonist for miniature pigs’combined anaesthetic were compared, which had further provided the rationale for antagonistic mechanisms.These datas were analyzed with pharmacokinetic computer program3p87. The results of atipamezole showed that the concentration-time course in plasma could be described by a two-compartment open model with first order absorption after the experimental miniture pigs were injected intramuscularly atipamezole. Its theoretical equation was follows: C(t)=1073.5771e-0.0983t+658.3057e-0.0009t-1731.8828e-0.8190t.The main pharmacokinetic parameters were those:α=0.0983min-1, β=0.0009min-1, Ka=0.8190min-1, K12=0.0554min-1, K21=0.0416min-1, K10=0.0022min-1,T1/2Ka=1.1037min, Ti/2α=11.0569min, T1/2β=875.42181min, AUC=797958.8360pg·min·mL-1, CL(s)=0.1682L/kg/min, Tp=9.5440min.It could be seen that atipamezole was absorbed rapidly by miniature pigs, and was widespreadly distributed. But its elimination rate was very slow.The concentration-time course of atipamezole in specificity antagonist for miniature pigs’ combined anaesthetic combination in plasma can also be described by a two-compartment open model with first order absorption. The theoretical equation and the main pharmacokinetic parameters were as follows: C(t)=2735.4728e-0.0628t+318.9999e-0.0010t-3054.4727e-0.1414t.The main pharmacokinetic parameters were those:a=0.0628min-1,β=0.0010min-1, Ka=0.1414mm-1, K12=0.0429min-1, K21=0.0175min-1, K10=0.0033min-1, T1/2Ka=5.5311min, T1/2α=;16.6795min, T1/2β=1238.1812min, AUC=508779.7352pg·min·mL-1, CL(s)=0.3274L/kg/min, Tp=16.5271min.The pharmacokinetic results showed:after the experimental miniature pigs were administrated atipamezole intramuscularly, atipamezole could be absorbed quickly, distributed widely and eliminated slowly.But when the experimental miniature pigs were administrated specificity antagonist for miniature pigs’combined anaesthetic intramuscularly, atipamezole was absorbed slower, but eliminated faster. That was because the metabolism of atipamezole in the combination in miniature pigs’plasma was influenced by other ingredients. Their absorptions and distributions were getting slower, and its T1/2β prolonged. But the establishment of the compartment model and the distribution of decay curve of concentration-time in plasma were not influenced.Compared with the results of blood drug level and pharmacodynamic action, the antagonistic effects of specificity antagonist for miniature pigs’combined anaesthetic was better than atipamezole alone with the influence of other drugs. But that was not with one accord with the results of their pharmacokinetics completely. It provided theory evidence for specificity antagonist for miniature pigs’combined anaesthetic’s antagonistic mechanisms, and ensured its safety for clinical application. |
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