左氧氟沙星人体内外相关性研究

Studies on Correlation between Dissolution in Vitro and Absorption in Vivo of Levofloxacin Tablets

目的研究两种左氧氟沙星片剂的体内-体外相关性。方法用不同转速测定两种左氧氟沙星片剂(分别由A,B两厂生产)的体外溶出度。采用反相高效液相色谱法测定18名健康志愿受试者单剂量口服两种左氧氟沙星片后的血药浓度,用3P97软件计算药动学参数,Wagner-Nelson法计算药物的体内吸收百分数,并分析体内外相关性。结果两厂生产的左氧氟沙星片剂在体内生物等效。以50,75,100r.min-1进行左氧氟沙星片体外溶出结果均符合《中国药典》2005年版要求。其中,以50r.min-1转速所作的体外溶出结果与体内生物利用度相关,回归方程为A:fa=2.0176ft+0.7279,r=0.957(P<0.05)。B:fa=1.8929ft+0.7749,r=0.955(P<0.05)。结论体外溶出试验与体内生物利用度有良好的体内外相关性,可用体外溶出度来控制制剂质量。

OBJECTIVE To investigate the relationship between dissolution in vitro and absorption in vivo of levofloxacin tablets from two pharmaceutical coorperations（A and B）. METHODS The dissolution of levofloxacin was determined in vitro according to Chinese pharmacopoeia （2005ed Part Ⅱ） with different rotation speed. Levofloxacin concentration in plasma was determined by RP-HPLC after a single dose of oral levofloxacin tablets given to 18 healthy male volunteers. Their pharmacokinetic parameters were obtained by 3P97 program,and the absorption percentage was calculated according to Wangner-Nelson formula. RESULTS The two preparations were bioequivalent. The dissolution parameters of levofloxacin tablets with different rotation speed （50,75 and 100 r·min^-1 ） all met the requirement of Chinese pharmacopoeia. The linear regressive equation was established between the absorption percentage in vivofa and accumulate release percentage in vitro （50 r·min^-1 ） ft of levofloxacin tablets as A ：fa = 2. 017 6ft ＋ 0. 727 9, r = 0. 957 （ P 〈 0. 05 ） ; B .fa = 1. 892 9ft ＋ 0. 774 9, r = 0. 955 （ P 〈 0. 05 ）. CONCLUSION There was a significant relationship between absorption in vivo and in vitro.