盐酸达泊西汀在中国男性志愿者中的药动学研究  

Pharmacokinetics of dapoxetine hydrochloride in Chinese healthy male volunteers

作　　者：司天梅[1] 刘薏[1] 苏允爱[1] 孙丽丽[1] 郭春梅[1] 张鸿燕[1] 舒良[1] 

机构地区：[1]北京大学精神卫生研究所,卫生部精神卫生学重点实验室,北京100083

出　　处：《中国新药杂志》2009年第22期2138-2142,共5页Chinese Journal of New Drugs

摘　　要：目的：研究中国男性健康志愿者单次口服不同剂量达泊西汀片的体内药动学特点。方法：24名健康男性受试者,被随机分为两组,分别单次空腹口服达泊西汀片,剂量分别为30 mg或60 mg。用高效液相色谱质谱质谱联用法测定血浆中的达泊西汀及其代谢产物去甲达泊西汀和达泊西汀-N-Oxide（N-氧化-达泊西汀）浓度,根据每个实际取血时间的药物浓度,用非房室模型计算达泊西汀及其代谢产物的药动学参数。结果：2剂量组受试者人口学资料相似,研究依从性良好,全部完成研究。口服盐酸达泊西汀片后,达泊西汀可以很快被吸收,随后是一个二相消除过程。药动学表现为线性药动学特点,单次口服达泊西汀30 mg和60 mg的主要药动学参数是：Cmax分别为（204.0±71.4）和（396.0±27.2）μg.L-1;Tmax分别为（1.02±0.39）和（1.07±0.28）h;t1/2分别为（15.0±7.2）和（15.4±5.8）h;AUC0-24分别为（901±338）和（1 598±740）μg.h.L-1,AUC0~∞分别为（1 078±508）和（2 022±1 107）μg.h.L-1。60 mg剂量组药动学参数经过剂量标准化为30 mg后，两组的药动学参数完全一致。口服30mg和60mg剂量组母体药物与代谢产物的Cmax比 值（达泊西汀／代谢产物）分别是：N一氧化一达泊西汀（3．020±0．997）和（2．44±1．14），去甲达泊西汀（23．8±3．57）和（20．3±5．54）；AUC0～∞。的比值分别是：N-氧化-达泊西汀（0．794±0．279）和（0．670±0．292），去甲达泊西汀（7．99±1．79）和（8．28-．I-2．21）。药动学参数的个体间差异较大，CV％最大值为75．4％。整个研究过程中，耐受性良好，常见的不良反应是短暂轻度的头晕和恶心，均在研究结束前缓解。结论：中国健康男性受试者单次口服不同剂量盐酸达泊西汀的药动学与在其他人种的研究结果相似，具有线性药动学特点，耐受性良好。Objective：To explore the pharmacokinetics of dapoxetine hydrochloride tablets after a single oral administration in healthy Chinese male volunteers.Methods：24 subjects were randomly assigned to receive either a single oral dose of 30 mg or 60 mg dapoxetine.Sequential blood samples were collected,dopaxetine and its metabolites,desmethyldapoxetine,and dapoxetine-N-oxide in plasma were determined by a validated high performance liquid chromatography with MS/MS.The pharmacokinetic parameters were calculated based on individual plasma concentration with noncompartmental analysis. Results： The demographic and baseline characteristics of subjects were well balanced between the 2 treatment groups. There were no early withdrawals and all 24 subjects completed the study. There was a rapid absorption of dapoxetine followed by abiphasic elimination of dapoxetine and its metabolites. Both the Cmax and AUC of dapoxetine were proportional to dose following oral administration of single doses of 30 mg and 60 mg. The main pharmacokinetic parameters following oral administration of single doses of 30 mg and 60 mg were： Cmax （204.0 ± 71.4） and （396.0 ± 27.2） μg·L-1, Tmax （ 1.02 ± 0. 39） and（ 1.07 ± 0.28 ） h, t1/2 （ 15.0 ± 7.2） and （ 15.4 ± 5.8 ） h, AUC0-24 （ 901±338 ） and （ 1 598 ± 740 ） μg·h·L-1, and AUC0～∞（1 078±508） and（2 022 ± 1 107）μg·h·L-1. The dose-normalized AUCs and Cx of dapoxetine and its metabo- lites were similar. The ratios of parent compound to metabolites following oral administration of single doses of 30mg and 60 mg dapoxetine were as follows ： Cmax of N-oxide-dapoxetine （3. 020 ± 0. 997 ） and （2.44 ± 1.14）, Cmax of desmethyldapoxetine （ 23.8 ± 3.57 ） and （ 20. 3 ± 5.54 ）, AUC0-∞ of N-oxide-dapoxetine （ 0. 794 ± 0. 279 ） and （0. 670 ±0. 292）, AUC0-∞ of desmethyldapoxetine （7.99 ± 1.79）and（8.28 ±2.21 ）. The inter-subject variabili- ty was larger,the maximal CV% was 75.4%. The drug was well-tolerated

关 键 词：盐酸达泊西汀片 高效液相质质联用色谱法 药动学 

分 类 号：R945.2[医药卫生—微生物与生化药学] R969.1[医药卫生—药剂学]