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目的建立HPLC-MS/MS测定人体血浆齐墩果酸(OA)浓度分析方法,探讨人体药动学特征。方法18例健康志愿者按随机分组自身交叉对照试验设计,口服OA普通片剂和分散片剂,采取受试者血样测定血药浓度,计算药动学参数,并用多元线性逐步回归分析药品暴露与各时间点血浆药物浓度的相关关系。结果根据药时数据用非房室模型进行药动学计算,得OA片和分散片的主要药动学参数:ρmax(18.9±8.0)和(17.8±7.5)μg.L-1;tmax(2.9±1.2)和(2.5±1.0)h;AUC0-48(112.2±56.6)和(109.7±41.6)μg.h.L-1;t1/2(12.3±9.0)和(16.1±12.1)h;MRT(13.6±8.6)和(18.3±11.8)h。分散片相对于普通片剂的人体生物利用度为(111.4±44.0)%。经多元线性逐步回归分析,AUC与ρ8-ρ48各呈良好相关性(r>0.7,P<0.01),并得出有限浓度值计算药品暴露量的线性回归方程式。结论OA人体药动学参数对临床用药有指导意义,有限的血样采集和浓度测定可以准确估算药品暴露程度。
OBJECTIVE To establish a method for the determination of the concentration of oleanolic acid (OA) in human plasma by HPLC-MS / MS and investigate the pharmacokinetic characteristics of human body. Methods Eighteen healthy volunteers were randomized to receive randomized controlled trials. Oral OA tablets and dispersible tablets were taken orally. Blood samples were taken for determination of plasma drug concentration. Pharmacokinetic parameters were calculated. Multivariate linear stepwise regression analysis The correlation of plasma drug concentration at each time point. Results The pharmacokinetic parameters of OA tablets and dispersible tablets were calculated according to pharmacokinetic data using non-compartmental model: ρmax (18.9 ± 8.0) and (17.8 ± 7.5) μg.L-1; tmax (2.9 ± 1.2 and ± 2.5 ± 1.0 h; AUC0-48 (112.2 ± 56.6) and (109.7 ± 41.6) μg.hL-1; t1 / 2 and 12.3 ± 9.0 and 16.1 ± 12.1 h; ± 8.6) and (18.3 ± 11.8) h. The bioavailability of dispersible tablets relative to conventional tablets was (111.4 ± 44.0)%. By multiple linear stepwise regression analysis, AUC and ρ8-ρ48 showed good correlation (r> 0.7, P <0.01), and obtained a linear regression equation for the calculation of drug exposure with a finite concentration value. Conclusion OA human pharmacokinetic parameters are instructive for clinical use. Limited blood sample collection and concentration determination can accurately estimate drug exposure.