磷酸可待因缓释片人体多剂量药动学及生物利用度

Multiple dose pharmacokinetics and bioavailability of codeine phosphate sustained release tablets in cancer patients

目的：研究磷酸可待因缓释片在肿瘤患者体内的多剂量达稳态药动学和生物利用度。方法：采用RP-HPLC法测定可待因的血药浓度，研究10名肿瘤患者多剂量口服磷酸可待因缓释片及 普通片达稳态后的药动学及相对生物利用度。结果：多剂量口服 缓释片及普通片达稳态后，AUCss0→τ分别为（599.8± 137.9）和（242.4±51.8） ng·h·ml-1；Tmax分别为（ 4.5±0.5）和（2.2±0.7） h，Cmax分别为（75.0±15.1 ）和（80.6±16.4） ng·ml-1，Cmin分别为（30.7±1 3.0）和（15.7±5.5） ng·ml-1，DF%分别为（91.8±19.1 ）%和（162.5±35.2）%，两种制剂的AUCss0→τ、Tma x、Cmin、DF%差异均有显著性（P<0.05）。磷酸可待因缓释 片相对生物利用度为（123.6±8.1）%。结论：磷酸可待因缓释片在多剂量给药时具有显著的缓释特性。

：OBJECTIVE To study the multiple dose bioavailability and pharmacokinetics of codeine phosp hate sustained release tablets. METHODS The plasma concentration of codeine was determined by RP-HPLC,steady state phar macokinetcs in 10 cancer patients after multiple oral administration of the tab lets and conventional tablets was studied. RESULTS Cmax of sustained release tablets and conventional tablets was （75. 0±15.1） and （80.6±16.4） ng·ml-1; Cmin was （30.7±13.0） and （15.7±5.5） ng·ml-1;Tmax w as （4.5±0.5） and （2.2±0.7） h;AUCss0→τ wa s （599.8±137.9） and （242.4±51.8） ng·h·ml-1,DF% was （91.8±19.1）% and （162.5±35.2）%,respectively.The resul ts of statistical analysis showed significant difference of Tmax、C min、AUCss0→τ and DF% between the two preparation s.The relative bioavailability of codeine phosphate sustained release tablets w as (123.6±8.1）%.CONCLUSIONS The codeine phosphate sustained release tablets have significant sustained relea se feature in the case of multiple oral dose.