地夫可特片在健康中国受试者体内药代动力学研究  

Pharmacokinetics of deflazacort tablets in healthy Chinese volunteers

作　　者：丁雯[1] 丁黎[1] 李文博[1] 潘虹[1] 林宏达[1] 

机构地区：[1]中国药科大学药物分析教研室,江苏南京210009

出　　处：《药学学报》2014年第6期921-926,共6页Acta Pharmaceutica Sinica

摘　　要：地夫可特为前体药物，口服给药后迅速吸收并代谢为活性产物21-羟基地夫可特（21-OH DFZ）。本文研究健康中国受试者单次和多次口服地夫可特片后21-OH DFZ的药代动力学特征。12名健康受试者，男女各半，按3×3拉丁方设计分别餐后单次交叉口服地夫可特片6、12和24mg，两次服药间的清洗期为1周。三周期单次给药结束后，经过1周清洗期进行多次给药试验，每日一次餐后15服地夫可特片12mg，连续服药7天。受试者餐后单次口服地夫可特片6、12和24mg后21-OHDFZ的Cmax分别为（37．74±11．6）、（61．54±17．7）和（123±23）ng·mL-1，t1/2分别为（1．904±0．32）、（1．964±0．27）和（2．134±0．34）h，AUC0-14h分别为（96．64±25．9）、（1904±44）和（4224-107）ng·h·mL-1。多次给药达稳态后，21-OH DFZ的稳态平均血药浓度Gav为（7．004±1．66）ng·mL-1，稳态血药浓度波动度DF为7．74±1．2。结果表明，口服地夫可特片6～24mg剂量内，21-OH DFZ在健康受试者体内呈线性药动学特征，药动学特征不存在性别差异，多次给药后药物在体内无蓄积。Deflazacort （DFZ, a prodrug） is well absorbed and rapidly metabolized into the active metabolite 21-hydroxydeflazacort （21-OH DFZ） after oral administration. The aim of this study is to evaluate the pharmacokinetic properties of 21-OH DFZ in healthy Chinese volunteers after a single and multiple oral administration of DFZ tablets under fed condition. Twelve volunteers （six males and six females） were administered a single dose of 6 mg or 12 mg or 24 mg of DFZ in three different periods separately, according to the 3 × 3 Latin square design. Between each administration period there was a washout period of one week. The multiple-dose study of 12 mg dose DFZ per day for 7 consecutive days was started after a 1 w washout period when the single-dose study completed. The pharmacokinetic parameters of 21-OH DFZ after the single oral administration of 6 mg, 12 mg and 24 mg DFZ tablets were as follows： （37.7 ± I1.6）, （61.5± 17.7） and （123±23） ng.mL-1 for Cmax; （1.90±0.32）, （1.96±0.27） and （2.13±0.34） h for tl/2; （96.6＋25.9）, （190±44） and （422 ± 107） ng·h·mL-1 for AUCH4 h, respectively. After the multiple dose administration, the mean plasma concentration at steady-state Cav was （7.00 ± 1.66） ng·mL-1 and the degree of plasma concentration fluctuation DF was 7.7± 1.2. The results showed that the pharmacokinetic characteristics of 21-OH DFZ in healthy Chinese volunteers were linear over the dose range of 6 to 24 mg. No significant gender differences were found in the pharmacokinetics of 21-OH DFZ in healthy Chinese volunteers. After the multiple dose administration of 12 mg DFZ for 7 d, no accumulation of21-OH DFZ in healthy Chinese volunteers was observed.

关 键 词：21-羟基地夫可特 地夫可特 药代动力学 

分 类 号：R969[医药卫生—药理学]