硫酸沙丁胺醇大鼠在体肠吸动力学研究

目的研究硫酸沙丁胺醇在大鼠各肠段的吸收动力学特征。方法采用大鼠在体肠回流法进行动力学试验,从吸收部位、药物浓度、pH值等方面对药物在体内的各个肠段的吸收特性进行研究。结果硫酸沙丁胺醇在大鼠肠道中的吸收不受药物浓度、回流介质pH值等的影响,在分肠段试验中,吸收速率常数Ka(1/h)依次为十二指肠0.052,空肠0.046,回肠0.042,结肠0.030,结肠的吸收显著低于十二指肠、空肠和回肠段;在pH5.4~7.8回流介质中吸收无显著差异,在50~200μg/mL浓度范围内,药物吸收量与浓度呈线性关系。结论硫酸沙丁胺醇在大鼠体内各肠段均有吸收,吸收机制以被动扩散为主,适于制成Tlag<5 h的口服迟释制剂。

Study on the absorption kinetics of salbutamolin rat's intestine in situ

Objective To explore the absorption characteristics and mechanism of salbutamol for various intestinal segments.Methods The absorption kinetics and absorption site in intestine were investigated by in situ perfusion method in rats.The effect of different absorption sites,drug concentration and pH value of solvents were investigated.Results The absorption rate(Ka)was 0.052(1/h)in duodenum,0.046(1/h)in jejunum,0.042(1/h)in Ileum and 0.030(1/h)in colon.The absorption percentage in colon was lower than in duodenum,jejunum and ileum.The parameters of absorption had no significant deviations when drug was dissolved into different media whose pH value was 5.4～7.8.The linear ranges of Salbutamol was 50～200 μg/mL.Conclusion The mechanism of absorption conforms to the passive diffusion primarily.The drug could be absorbed in any segment of intestine.It can be used as delay released dosage form and the compatible lag-time is less than 5 h.