国产丙戊酸钠无糖口服液人体生物等效性研究

Study on bioequivalence of domestic sodium valproic oral liquid in healthy volunteers

目的 :评价国产丙戊酸钠无糖口服液和进口丙戊酸钠糖浆两种制剂的生物等效性。方法 :2 0例健康男性志愿者双周期随机交叉口服单剂量 10 0 0mg(2 5mL)国产丙戊酸钠无糖口服液和进口丙戊酸钠糖浆两种制剂 ,分别于服药前及服药后 0 .33,0 .6 7,1,1.5 ,2 ,4 ,8,12 ,2 4 ,36 ,4 8及 72h采集血样。用高效液相 荧光色谱法测定血清中丙戊酸钠的浓度 ,并对试验数据进行处理。结果 :单次口服国产及进口丙戊酸钠制剂的Cmax分别为 (112 .6 5±16 .91)和 (110 .2 2± 15 .2 0 ) μg·mL- 1 ;Tmax分别为 (0 .86± 0 .38)和 (1.0 9± 0 .4 8)h ;AUC0～ 72h 分别为 (1980 .2 4±2 75 .82 )和 (195 0 .11± 30 5 .6 0 ) μg·h·mL- 1 ;AUC0～∞ 分别为 (2 0 88.19± 313.2 5 )和 (2 0 75 .30± 36 7.5 8) μg·h·mL- 1 ;单次口服国产丙戊酸钠无糖口服液的相对生物利用度F0～ 72h 为 (10 2 .96± 15 .37) % ,F0～∞ 为 (10 2 .2 5±15 .6 1) %。结论 :单次口服国产丙戊酸钠无糖口服液和进口丙戊酸钠糖浆具有生物等效性。

Objective:To evaluate the relative bioavailability and bioequivalence of domestic sodium valproic oral liquid and imported sodium valproic syrup in healthy volunteers.Methods:A single oral administration of 1 000mg(25mL) domestic sodium valproic oral liquid and imported sodium valproic syrup were given to 20 healthy male volunteers in randomized crossover study respectively. A high performance liquid chromatographic assay with fluorimetric detection was developed to determine the concentration of sodium valproic in human serum. The data were analyzed by 3P97 program.Results:The pharmacokinetics parameters after a single oral administration of 1 000mg(25mL) domestic sodium valproic oral liquid and imported sodium valproic syrup were as follows: C max (112.65±16.91 ) and (110.22± 15.20)μg·mL -1 ; T max (0.86±0.38 )and(1.09±0.48)h; AUC 0～72h (1 980.24±275.82 )and (1 950.11±305.60)μg·h·mL -1 ; AUC 0～∞ (2 088.19±313.25) and (2 075.30±367.58)μg·h·mL -1 ; F 0～72h (102.96±15.37)%, F 0～∞ (102.25±15.61)% respectively. Variance analysis and two one sided test were performed to parameters: C max , AUC 0～72h , AUC 0～∞ .There were no significant difference.Conclusion:The relative bioavailability of single oral administration group was (102.96± 15.37)%. The two preparations were of bioequivalence.