国产与进口噻氯匹定的药动学及生物利用度比较研究

 目的：研究国产噻氯匹定片剂与进口同种产品的生物利用度及其药动学特性。方法：8名健康成年受试者，男女各半，随机交叉分组试验法分别按每12 hpo250 mg国产和进口噻氯匹定连续5个剂量。采用作者建立的HPLC测定血药浓度。结果：国产和进口片剂的动力学参数：c_max(ss)分别为2.08±1.24 mg/L和1.66±0.37 mg/L，T_max分别为0.97±0.42 h和1.22±0.38 h，β分别为0.088±0.026 h^-1和0.080±0.040 h^-1，表观分布容积〖WTBX〗V〖WTBZ〗d/F分别为73.60±21.50 L和91.96±29.80 L，吸收速率常数K₀₁分别为5.192±5.489 h^-1和5.851±5.832 h^-1；稳态后梯形法求得的AUC(48～60 h)分别为6.32±1.21 (h·mg)/L和6.24±1.80 (h·mg)/L。结论：两种片剂的药动学参数无统计学差异(〖WTBX〗P〖WTBZ〗＞0.05)。与进口片剂相比，国产片剂的平均相对生物利用度为99.97%±26.51%。

Pharmacokineticsandbioavailabilityofdomesticandimportedticlopidineinhealthyvolunteers

OBJECTIVE:Pharmacokinetics and bioavailability of domestic and imported ticlopidine tablets were compared in healthy volunteers after oral administration.METHODS:Eight healthy volunteers were given orally 500 mg tablets twice a day for 5 doses.The blood samples were collected after the 5th dose and ticlopidine levels were determined by HPLC.The PCNONLIN software (v.4.2) and non-compartment model analysis were used for the calculation of pharmacokinetics and relative-bioavailability, respectively.RESULTS:The pharmacokinetic parameters of domestic and imported tablets were T_max=0.97±0.43 h and 1.22±0.38 h,c_max(ss)=2.08±1.241 mg/L and 1.66±0.37 mg/L,T_1/2(β)=8.53±2.55 h and 12.18±8.08 h,β=0.088±0.026 h^-1 and 0.080±0.040 h^-1,the Vd/F were 73.60±21.50 L and 91.96±29.80 L,respectively.The AUCτ calculated by the trapezoidal rule was 6.19±1.49(h·mg)/L and 6.36±1.39 (h·mg)/L,respectively.And the F of domestic vs imported was 99.97±26.51%.CONCLUSION:There was no significant difference (P＞0.05) between domestic and imported ticlopidine tablets in the phamacokinetic behavior and bioavailabilities in humans.