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目的研究健康受试者口服受试制剂萘普生钠缓释片和参比制剂萘普生钠胶囊的相对生物利用度和生物等效性。方法18名男性健康志愿者随机分成2组,先后单剂量、多剂量自身对照交叉口服受试制剂和参比制剂后采血,采用HPLC法测定血药浓度,计算药动学参数,并考察受试制剂的体内外相关性。结果单剂量口服受试片剂后的药动学参数分别为:tmax为(3.11±0.96)h,ρmax为(63.48±9.48)mg.L-1,t12为(17.73±1.79)h,MRT为(24.88±3.03)h,AUC0→t为(1 208.99±169.75)mg.h.L-1,,AUC0→∞为(1 285.04±192.91)mg.h.L-1;单剂量口服参比胶囊后的药动学参数分别为:tmax为(1.85±1.00)h,ρmax为(73.99±10.78)mg.L-1,t12为(18.26±2.60)h,MRT为(23.76±3.31)h,AUC0→t为(1 222.82±157.03)mg.h.L-1,AUC0→∞为(1 301.44±185.81)mg.h.L-1;多剂量口服受试片剂后的药动学参数分别为:tmax为(2.61±0.70)h,ρmax为(76.49±9.57)mg.L-1,ρmin为(23.54±4.46)mg.L-1,AUCs0s→24h为(982.86±117.49)mg.h.L-1,ρav为(40.95±4.90)mg.L-1,DF为(130.47±24.05)%;多剂量口服参比胶囊后的药动学参数分别为:tmax为(1.55±0.90)h,ρmax为(68.71±7.62)mg.L-1,ρmin为(35.33±4.68)mg.L-1,AUC0ss→12h为(564.20±68.28)mg.h.L-1,ρav为(47.02±5.69)mg.L-1,DF为(79.29±15.50)%。结论经方差分析、双单侧t检验表明两制剂具有生物等效性,且受试片剂具有缓释特征。受试制剂在人工肠液中前4 h的释放行为与体内的吸收百分率有较好的相关性。
Objective To study the relative bioavailability and bioequivalence of naproxen sodium sustained-release tablets and reference preparation naproxen sodium capsules for oral health test. Methods Eighteen male healthy volunteers were divided into two groups at random. One single dose and multiple doses of self-control were taken after oral administration of the test preparation and the reference preparation. The blood concentration was determined by HPLC and the pharmacokinetic parameters were calculated. In vivo and in vitro relevance of the formulation. Results The pharmacokinetic parameters of single-dose oral tablets were: tmax was (3.11 ± 0.96) h, ρmax was (63.48 ± 9.48) mg.L-1, t12 was (17.73 ± 1.79) h, MRT was (24.88 ± 3.03) h, the AUC0 → t was (1 208.99 ± 169.75) mg.hL-1, and the AUC0 → ∞ was (1 285.04 ± 192.91) mg.hL-1. The parameters of learning were as follows: tmax was (1.85 ± 1.00) h, ρmax was (73.99 ± 10.78) mg.L-1, t12 was (18.26 ± 2.60) h and MRT was (23.76 ± 3.31) 1 222.82 ± 157.03) mg.hL-1, and the AUC0 → ∞ was (1 301.44 ± 185.81) mg.hL-1. The pharmacokinetic parameters of the multi-dose oral test tablets were as follows: tmax was (2.61 ± 0.70) h, ρmax was (76.49 ± 9.57) mg.L-1, ρmin was (23.54 ± 4.46) mg.L-1, AUCs0s → 24h was (982.86 ± 117.49) mg.hL-1 and ρav was (40.95 ± 4.90) mg.L-1 and DF were (130.47 ± 24.05)%, respectively. The pharmacokinetic parameters of multidose oral reference capsules were as follows: tmax was (1.55 ± 0.90) h and ρmax was (68.71 ± 7.62) 1, ρmin was (35.33 ± 4.68) mg.L-1, AUC0ss → 12h was (564.20 ± 68.28) mg.hL-1, ρav was (47.02 ± 5.69) mg.L-1 and DF was (79.29 ± 15.50) %. Conclusion By ANOVA, two-sided one-tailed t tests showed that the two preparations were bioequivalent and the sustained release tablets had the characteristics of sustained release. The release of test preparations in the first 4 h in artificial intestinal juice had a good correlation with the percentage absorption in vivo.