复方缓释胶囊中氯苯那敏的人体药物代谢动力学及生物等效性研究

Pharmacokinetics and bioequivalence of chlorpheniramine in 2 compound controlled-release capsules in healthy volunteers

目的研究美敏伪麻缓释胶囊和盐酸伪麻黄碱缓释胶囊中氯苯那敏在健康人体内的药物代谢动力学过程和生物等效性。方法本试验采用双周期自身随机交叉试验设计。21名受试者分为2组,先后口服2种复方缓释胶囊,2次用药间隔14 d,采用HPLC-MS/MS测定。结果试验药物和参比药物中氯苯那敏的Cmax为（5.05±1.39）ng·mL^-1和（5.41±1.45）ng·mL^-1;tmax为（4.50±1.89）h和（4.25±1.55）h;AUC0-t为（136.50±47.52）h·ng·mL^-1和（145.40±46.28）h·ng·mL^-1;AUC0-inf为（160.85±63.80）h·ng·mL^-1和（168.72±56.26）h·ng·mL^-1;t1/2为（23.26±6.91）h和（22.68±6.41）h;相对生物利用度F0-t和F0-inf分别为（93.2±19.0）%和（93.5±18.4）%。Cmax、AUC0-t、AUC0-inf比值的90%可信区间分别为87.07%-99.28%、85.95%-101.04%和86.64%-101.18%。结论美敏伪麻缓释胶囊和盐酸伪麻黄碱缓释胶囊中的氯苯那敏在中国健康男性受试者体内具有生物等效性。

Objective To study the pharmacokinetics and bioequivalence of chlorpheniramine in 2 compound controlledrelease capsules. Methods In a randomized 2-period crossover study, 21 healthy male volunteers received a single dose of test capsules or reference capsules in sequence with a washout period of 14 days. The serum concentrations were detected by HPLC-MS/MS method. Results The main pharmacokinetic parameters of chlorpheniramine in the test capsules and reference capsules were： Cmax（5.05±1.39） and（5.41±1.45） ng·mL^-1; tmax（4.50±1.89） and（4.25±1.55） h; AUC0 - t（136.50±47.52） and（145.40±46.28） h·ng·mL^- 1; AUC0 - inf（160.85±63.80） and（168.72±56.26） h·ng·mL^- 1; t1/2（23.26±6.91）h and（22.68±6.41）h; F0 - t（93.2±19.0） %; F0 - inf（93.5±18.4）%. The 90%confidence intervals of ratios of Cmax, AUC0 - t and AUC0 - inf were 87.07%- 99.28%, 85.95%- 101.04% and 86.64%- 101.18%, respectively. Conclusion Chlorpheniramine in the 2 compound controlled-release capsules are bioequivalent.