Xie Feifan, Cheng Zeneng, Li Sanwang, Liu Xingling, Guo Xin, Yu Peng, Gu Zhenkun
School of Pharmaceutical Sciences, Central South University, Changsha, PR China.
J Clin Pharmacol. 2014 Jun;54(6):688-95. doi: 10.1002/jcph.261. Epub 2014 Jan 22.
Benfotiamine is a lipid-soluble thiamine precursor which can transform to thiamine in vivo and subsequently be metabolized to thiamine monophosphate (TMP) and thiamine diphosphate (TDP). This study investigated the pharmacokinetic profiles of thiamine and its phosphorylated metabolites after single- and multiple-dose administration of benfotiamine in healthy Chinese volunteers, and assessed the bioavailability of orally benfotiamine administration compared to thiamine hydrochloride. In addition, concentration of hippuric acid in urine which is produced in the transformation process of benfotiamine was determined. The results showed that thiamine and its phosphorylated metabolites exhibited different pharmacokinetic characteristics in plasma, blood and erythrocyte, and one-compartment model provided the best fit for pharmacokinetic profiles of thiamine. The transformation process of benfotiamine to thiamine produced large amount of hippuric acid. No accumulation of hippuric acid was observed after multiple-dose of benfotiamine. Compared to thiamine hydrochloride, the bioavailability of thiamine in plasma and TDP in erythrocyte after oral administration of benfotiamine were 1147.3 ± 490.3% and 195.8 ± 33.8%, respectively. The absorption rate and extent of benfotiamine systemic availability of thiamine were significantly increased indicating higher bioavailability of thiamine from oral dose of benfotiamine compared to oral dose of thiamine hydrochloride.
苯磷硫胺是一种脂溶性硫胺素前体，可在体内转化为硫胺素，随后代谢为硫胺素单磷酸酯（TMP）和硫胺素二磷酸酯（TDP）。本研究调查了健康中国志愿者单次和多次服用苯磷硫胺后硫胺素及其磷酸化代谢产物的药代动力学特征，并评估了口服苯磷硫胺与盐酸硫胺相比的生物利用度。此外，还测定了苯磷硫胺转化过程中产生的尿中马尿酸的浓度。结果表明，硫胺素及其磷酸化代谢产物在血浆、血液和红细胞中表现出不同的药代动力学特征，一室模型最适合硫胺素的药代动力学曲线。苯磷硫胺向硫胺素的转化过程产生了大量马尿酸。多次服用苯磷硫胺后未观察到马尿酸的蓄积。与盐酸硫胺相比，口服苯磷硫胺后血浆中硫胺素和红细胞中TDP的生物利用度分别为1147.3±490.3%和195.8±33.8%。苯磷硫胺的吸收速率和硫胺素全身可用性程度显著增加，表明与口服盐酸硫胺相比，口服苯磷硫胺的硫胺素生物利用度更高。
