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目的建立高效液相色谱法测定莫达非尼血药浓度,并使用该方法进行莫达非尼不同剂型间的人体相对生物利用度和生物等效性研究。方法采用随机、开放、三制剂、三周期、二重3×3拉丁方设计,24名受试者随机分为6组,于不同周期分别服用受试制剂T1(片剂)、受试制剂T2(胶囊)、参比制剂R(分散片)各200mg。采用HPLC-UV法测定血样中莫达非尼的浓度,计算药物动力学参数并进行生物等效性评价。结果在0.125～20.0mg.mL-1莫达非尼浓度与峰面积线性关系良好(r=0.998)。受试制剂T1、T2、参比制剂R的主要药动学参数AUC0→24h分别为(73.6±18.0)、(70.9±12.8)、(72.4±16.7)mg.h.L-1;AUC0→∞分别为(81.8±22.6)、(78.8±16.2)、(79.8±20.4)mg.h.L-1;Cmax分别为(4.89±0.68)、(4.76±0.89)、(4.80±0.76)mg.L-1;tmax分别为(1.80±0.70)、(2.00±0.90)、(1.90±0.80)h;t1/2分别为(14.60±3.50)、(15.00±3.40)、(14.00±3.00)h。受试制剂T1的相对生物利用度为(101.8±11.8)%,受试制剂T2的相对生物利用度为(99.6±12.3)%。结论莫达非尼片剂及胶囊与莫达非尼分散片具有生物等效性。
OBJECTIVE To establish a method for the determination of modafinil in human plasma by high performance liquid chromatography (HPLC) and to study the relative bioavailability and bioequivalence of modafinil in different dosage forms. Methods Randomized, open, three-agent, three-cycle, double 3 × 3 Latin square design, 24 subjects were randomly divided into 6 groups, taking different doses of test preparation T1 (tablet), test preparation T2 (Capsule), reference formulation R (dispersible tablets) each 200mg. The concentrations of modafinil in blood samples were determined by HPLC-UV method, the pharmacokinetic parameters were calculated and the bioequivalence was evaluated. The results showed that there was a good linear relationship between the concentration of modafinil at 0.125 ~ 20.0mg.mL-1 and the peak area (r = 0.998). The main pharmacokinetic parameters AUC0 → 24h were (73.6 ± 18.0), (70.9 ± 12.8) and (72.4 ± 16.7) mg.hL-1 for T1, T2 and reference formulation R, respectively; AUC0 → ∞ were (81.8 ± 22.6), (78.8 ± 16.2) and (79.8 ± 20.4) mg.hL-1, respectively; Cmax were (4.89 ± 0.68), (4.76 ± 0.89) and (4.80 ± 0.76) mg.L- (1.80 ± 0.70), (2.00 ± 0.90) and (1.90 ± 0.80) h, respectively; t1 / 2 were (14.60 ± 3.50), (15.00 ± 3.40) and (14.00 ± 3.00) h, respectively. The relative bioavailability of test preparation T1 was (101.8 ± 11.8)%, and the relative bioavailability of test preparation T2 was (99.6 ± 12.3)%. Conclusion Modafinil tablets and capsules are bioequivalent to modafinil dispersible tablets.