口服脂溶性苯磷硫胺片与水溶性盐酸硫胺素片的生物利用度评价

Bioavailability assessment of the lipophilic benfotiamine as compared to a water-soluble thiamine hydrochloride after oral administration

目的：比较口服脂溶性苯磷硫胺片与水溶性盐酸硫胺素片的生物利用度。方法： 20名健康男性志愿者采用2×2交叉试验设计，分别单次给予 300 mg 苯磷硫胺片和 220 mg 盐酸硫胺片。给药后于不同时间点采集肘静脉血并收集 24 h 内的尿液。采用HPLC-Flu法测定血浆及红细胞中硫胺素及二磷酸硫胺素浓度。药动学参数采用WinNonlin软件计算，同时计算马尿酸各时间段的平均排泄速率。结果： 服用苯磷硫胺片和盐酸硫胺片后血浆中硫胺素的t1/2分别为（2.5±0.2）、（2.0±0.8） h；AUC0-24分别为（1763.1±432.7）、（182.0±93.8） μg·h·L-1；AUC0-∞分别为（1837.3±466.5）、（195.8±96.6） μg·h·L-1；Cmax分别为（568.3±122.0）、（70.5±46.2）μg/L；CL/F分别为（172.3±39.2）、（1831.7±705.0）L/h； Vd/F分别为（627.9±131.8）、（5419.1±3586.6）L。红细胞中二磷酸硫胺素的AUC0-24分别为（3212.4±740.7）、（881.8±316.2） μg·h·L-1。与盐酸硫胺相比，苯磷硫胺片中硫胺素的相对生物利用度F为（1147.3±490.3）%，二磷酸硫胺素的相对生物利用度F为（392.1±114.8）%。服用苯磷硫胺后0－4 h 时间段尿液中马尿酸的排泄速率较盐酸硫胺组有明显加快。结论：苯磷硫胺吸收迅速，相对生物利用度大于盐酸硫胺，给药后在 4 h 内全部转化为硫胺素。

AIM. To study the bioavailability of the lipophilic benfotiamine as compared to a water-soluble thiamine hydrochloride after oral administration. METHODS： A randomized, crossover study involving 20 healthy male volunteers was carried. Each subject was given 300 mg benfotiamine or 220 mg thiamine hydrochloride. Blood samples were collected at different times and 24 h urine samples were collected after administration. The concentrations of thiamine and thiamine diphosphat in plasma or erythrocyte were determined by HPLC-Flu. The main pharmacokinetic parameters were calculated using WinNonlin program and the mean excretion rate of hippuric acid in urine was also evaluated. RESULTS：The main pharmacokinetic parameters of thiamine in plasma after taking benfotiamine and thiamine hydrochloride were as follows： t1/2 were （2.5±0.2） and （2.0±0.8） h, respectively; AUC0-24 were （1763.1±432.7） and （182.0± 93.8） μg·h·L-1, respectively; AUC0-∞ were （1837.3± 466.5） and （195.8± 96.6） μg·h·L-1 , respectively; Cmax were （568.3 ±122.0） and （70. 5± 46.2） μg/L, respectively; CL/F were （172.3±39.2）and （1831.7±705. 0） L/h, respectively; Vd/F were （627.9 ± 131.8） and （5419.1 ± 3586.6） L, respectively. The AUC0-24 of thiamine diphosphat in erythrocyte after taking benfotiamine and thiamine hydrochloride was （3212.4 ± 740.7） and （881.8± 316.2） μg ·h · L-1, respectively. In comparison with thiamine hydrochloride, the relative bioavailabiiity of thiamine and thiamine diphosphat in benfotiamine were （ 1147.3±490.3） and （392.1 ± 114.8）%, respectively. The excretion rate of hippuric acid in urine in 4 h after taking benfotiamine was significantly accelerated than that after taking thiamine hydrochloride. CONCLUSION： Benfotiamine is absorbed quickly, and has better bioavailability than thiamine hydrochloride. It can be transformed to thiamine in 4 h after administration.