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目的 HPLC法观察改性钠基蒙脱石(NM)对盐酸雷尼替丁(RH)胶囊犬药代动力学的影响。方法随机分成8组(每组2只):RH对照组、RH/NM组、NM后3个不同时间(0.5,1.0,2.0 h)RH组、NM前3个不同时间(0.5,1.0,2.0h)RH组。交叉试验3周期。在给RH后0.25,0.5,1.0,1.5,2.0,3.0,4.0,5.0,6.0,8.0,10,12 h采血。HPLC法测定血浆雷尼替丁浓度,DAS软件计算主要药代动力学参数。结果RH的主要药代动力学参数:Cmax为(3.62±1.32)μg.mL-1,AUC0-t为(8.73±1.88)μg.mL-1.h,AUC0-∞为(9.38±2.35)μg.mL-1.h,MRT0-t为(2.90±0.15)h,t1/2z(3.82±3.13)h,Tmax为(0.917±0.376)h。NM后3个不同时间(0.5,1.0,2.0 h)RH组的Fr值分别为52.0%,73.1%,86.4%。NM前3个不同时间(0.5,1.0,2.0 h)RH组的Fr值分别为57.0%,64.8%,86.9%。RH/NM组的Fr值仅29.1%。结论改性钠基蒙脱石明显抑制盐酸雷尼替丁在犬体内的吸收,建议临床应避免给药间隔低于1 h,不仅避免NM过高地抑制RH在体内的吸收,并且能提高体内生物利用度。
Objective To observe the effect of modified sodium-based montmorillonite (NM) on the pharmacokinetics of ranitidine hydrochloride in dogs by HPLC. METHODS: The rats were randomly divided into 8 groups (2 in each group): RH control group, RH / NM group, RH group at 3 different time points (0.5, 1.0 and 2.0 h) h) RH group. Cross-test 3 cycles. Blood was collected 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10, 12 h after RH. The plasma concentration of ranitidine was determined by HPLC and the main pharmacokinetic parameters were calculated by DAS software. Results The main pharmacokinetic parameters of RH were (Cmax 3.62 ± 1.32) μg.mL-1, AUC0-t 8.73 ± 1.88 μg.mL-1.h and AUC0-∞ (9.38 ± 2.35) μg (2.90 ± 0.15) h, t1 / 2z (3.82 ± 3.13) h and Tmax was (0.917 ± 0.376) h, respectively. The Fr values of RH group were 52.0%, 73.1% and 86.4% at 3 different time points (0.5, 1.0 and 2.0 h) respectively. The Fr values of RH group were 57.0%, 64.8% and 86.9% respectively at the first 3 different time points (0.5, 1.0, 2.0 h). The value of Fr in RH / NM group was only 29.1%. Conclusion Modified sodium montmorillonite obviously inhibits the absorption of ranitidine hydrochloride in dogs. It is suggested that the administration should be avoided in less than 1 h in clinical practice, not only to prevent the excessive absorption of NM in vivo by NM, but also to improve the in vivo biological activity Utilization.