健康男性多次口服爱地那非片的药代动力学和安全性

Pharmacokinetics and safety of aildenafil tablets in healthy Chinese male subjects after multiple dose administration

目的研究中国男性健康受试者多次口服枸橼酸爱地那非片（治疗阴茎勃起功能障碍）的安全性和药代动力学。方法27名受试者随机分为30、45和60 mg 3个剂量组,每组9人,试验期间严密观察临床症状体征和不良事件,用LC-MS/MS测定多次服药后血浆中的药物浓度,并计算药代动力学参数。结果受试者多次口服枸橼酸爱地那非片30、45和60 mg后,其主要药代动力学参数：Cm ax分别为（256.6±106.6）、（435.7±115.4）和（918.6±442.5）ng.mL^-1;Cav分别为（57.2±26.1）、（95.0±28.9）和（247.6±137.0）ng.mL^-1;tm ax分别为（1.1±0.6）、（1.2±0.6）和（1.6±0.5）h;t1/2分别为（4.5±0.3）、（4.4±0.6）和（3.9±0.6）h;AUC0-24h分别为（1373.3±625.6）、（2280.1±693.6）和（5941.8±3288.4）ng.h.mL^-1;AUC0-36h分别为（1405.9±650.2）、（2314.6±710.3）和（6039.9±3 338.4）ng.h.mL^-1。药物不良反应主要为面色潮红、头痛或头晕等,程度均为轻度。结论连续3天,每天1次,口服枸橼酸爱地那非30-60 mg对健康受试者是安全的,爱地那非在体内无明显蓄积;在30、45 mg时,Cm ax和AUC0-t与剂量成比例增加;而在60 mg时,呈非线性药代动力学特征。

Objective To study the safety and pharmacokinetics of aildenafil citrate tablets after multiple doses in healthy Chinese male volunteers. Methods Twenty-seven healthy volunteers were randomly allocated into three groups, each group consisted of 9 subjects, were administed multiple doses of aildenafil citrate tablets at 30, 45 and 60 rag, respectively. The safety was assessed based on clinical Symptoms and adverse event. The concentrations of aildenafil in human plasma were determined by LC-MS/MS. The main pharmacokinetic parameters were calculated with WinNonLin 5.0 program. Results The pharmacokinetic parameters of aildenafil after multiple doses of 30, 45 and 60 mg were as follows：Cmax were （256. 6 ± 106.6）, （435.7 ± 115.4） and （918.6 ± 442.5） ng · mL^-1 ;Cav were （57.2 ±26. 1 ）, （95.0 ±28.9）and （247.6 ±137.0） ng·mL^-1;tmax were （1.1±0.6）, （1.2 ±0.6） and （1.6± 0,5） h;t1/2 were （4.5 ±0.3）, （4.4 ±0.65） and （3.9 ±0.6） h; AUC0-24hwere （1373.3±625.6）, （2280.1 ±693.6） and （5941.8± 3288.4） ng· h · mL^-1 ; AUC0-36h were （ 1405.9 ±650.2）, （2314.6± 710. 3） and （6039.9 ± 3338.4） ng · h · mL^-1 , respectively. There were no serious adverse events, the adverse events judged by the investigator to be related to aildenafil citrate tablets were flushing, headache or dizziness. Conclusion Aildenafil citrate tablets were safe in Chinese male healthy subjects after multiple doses of 30 -60 mg, qd for 3 days. There was not accumulation of aildenafil citrate tablet in plasma, Cmax and AUC0-t of aildenafil increased almost dose-proportionally between 30 and 45 mg, and became more than doseproportional with the 60 mg dose, the pharmacokinetics fit non-linear kinetic feature.