【摘要】 目的:研究地西泮鼻腔吸收的主要影响因素、吸收动力学及促透剂薄荷醇对其吸收的影响。方法:建立家兔在体鼻腔循环吸收的动物模型,取样时间为0、5、10、15、30、45、60、75、90 min,计算药物吸收速率常数K、吸收半衰期(t1/2)及药物吸收率。研究在鼻腔灌流液体积、循环液流速和pH值一定的条件下,地西泮的质量浓度、吸收促进剂薄荷醇对地西泮鼻腔吸收的影响。结果:在鼻腔灌流液体积为5 ml,循环液流速2.0 ml/min,循环液的pH值在5.9～6.1的中性吸收环境下,地西泮质量浓度在0.25～1.00 g/L时,随着地西泮质量浓度的增加,药物吸收速率常数K增加不明显,t1/2及药物吸收率变化不大;薄荷醇含量为0.2%时对地西泮鼻腔吸收有最佳的促进效果[药物吸收速率常数K为(0.442 4±0.002 3)/h],且能加快地西泮的吸收[t1/2为(0.32±0.07)h)],缩短地西泮的t1/2;0.2%～0.4%范围内,随薄荷醇质量浓度的增加,药物吸收速率常数K反而减小。结论:地西泮可以经鼻腔吸收,鼻腔吸收的机制为被动扩散;0.2%薄荷醇能促进地西泮的鼻腔吸收。更多还原

【Abstract】 OBJECTIVE:To study the factors associated with intranasal absorption of diazepam,its absorption kinetics and the effect of the penetration enhancer menthol on its absorption.METHODS:The in vivo nasal recirculation rabbit model was established.Sampling was scheduled at 0,5,10,15,30,45,60,75 and 90 min.Intranasal absorption rate constant K,t1/2(half time of absorption) and absorption rate were computed.Under a certain condition of nasal perfusate volume,circulation fluid flow rate and pH value,the effects of mass concentration of diazepam and the penetration enhancer menthol on intranasal absorption of diazepam were investigated.RESULTS:At a nasal perfusate volume of 5 ml,recirculation flow rate of 2 mL/min,pH value(of the circulation fluid) of 5.9-6.1(neutral absorption environment),the concentration of diazepam at a concentration range of between 0.25 g/L and 1.00 g/L,the increase of the concentration of diazepam was associated with insignificant increase of intranasal absorption rate constant(k) and insignificant change in t1/2(half time of absorption).At a content of 0.2%,menthol exhibited optimal promoting effect on the absorption of diazepam [k =(0.442 4±0.002 3)/h] and it contributed to the fast absorption of diazepam [t1/2 =(0.32±0.07)h] and shortening of t1/2 of diazepam;within the concentration range of 0.2%-0.4%,with menthol concentration increasing,k decreased.CONCLUSION:Diazepam can be absorbed intranasally.The mechanism underlying the intranasal absorption is passive diffusion.0.2% menthol could facilitate the intranasal absorption of diazepam.更多还原