萘普生钠缓释片人体药动学及生物等效性

Pharmacokinetics and bioequivalence of naproxen sodium sustained release tablets in healthy volunteers

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。

AIM To study the relative bioavailability and bioequivalence following oral administration of trial naproxen sodium sustained release tablets and reference naproxen sodium capsules in healthy volunteers. METHODS Eighteen healthy volunteers were orally given single dosing and multiple dosing of test and reference formulation in an open randomized cross-over test. The naproxen sodium concentration in plasma was determined by HPLC, and the pharmacokinetic parameters were calculated. The in vivo-in vitro correlation of test formulation was also investigated. RESULTS The parameters of the test and reference formulation after single dosing were as follows： tmax was （3.11 ± 0.96） h and （1.85± 1.00） h; ρmx was （63.48±9.48） mg·L^-1 and （73.99± 10.78） mg·L^-1; t1/2 was （17.73± 1.79） h and （18.26 ± 2.60） h; MRT was （24.88± 3.03） h and （23.76 ± 3.31） h; AUC0→t was （1 208.99 ± 169.75）mg·h· L^-1 and （1 222.82± 157.03） mg·h·L^-1; AUC0→∞ was （1 285.04± 192.91） mg·h·L^-1 and （1 301.44± 185.81） mg·h·L^-1, respectively. The parameters of the test and reference formulation after multiple dosing were as follows： tmax Was （2.61 ± 0.70） h and （ 1.55 ± 0.90） h; ρmax Was （76.49 ±9.57） mg·L^-1 and （68.71 ± 7.62） mg· L^- 1 ; ρmin Was （23.54±4.46） mg·L^-1 and （35.33 ±4.68） mg·L^-1; Pay was （40.95 ± 4.90） mg·L^-1 and （47.02± 5.69） mg· L^- 1 ; DF was （ 130.47 ± 24.05） % and （79.29 ± 15.50） %, respectively. AUC^SS 0→24h of test formulation was （982.86 ±117.49） mg·h· L^-1 and AUC^SS0→12h of reference formulation was （564.20 ± 68.28） rag· h· L^- 1. CONCLUSION The two formulations were bioequivalent and the test tablets have the property of sustained release. A good correlation of the trial naproxen sodium sustained release tablets is obtained between the in vitro release during 4 h in artificial intestinal juice and the in vivo absorption pereent.