Ma L, Cao Y, Chen L, Xiao Q, Yang J, Yang J
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China.
Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
Drug Res (Stuttg). 2015 Mar;65(3):125-32. doi: 10.1055/s-0034-1374599. Epub 2014 Apr 24.
Severe allergic reactions associated with the commercially available formulation of vitamin K1 injection (VKI) could be a result of polysorbate that was added to solubilize vitamin K1 (VK1). Hence, we sought to develop vitamin K1 lipid emulsion (VKLE) devoid of polysorbate, in order to reduce the clinical risk of severe allergic reactions. This study aims to evaluate the pharmacokinetics and pharmacodynamics of VKLE in comparison to VKI in rats.
Plasma concentration-time profiles of VK1 were investigated in rats after dosing VKLE or VKI at the range of 1-4 mg/kg. Tissue distribution of VKLE and VKI were investigated in rats at the dose of 2 mg/kg. The pharmacodynamics of VKLE and VKI were also studied by comparing their effects on coagulation factors (II/VII/IX/X) and prothrombin time in hypoprothrombinemic rats.
VKI demonstrated over-proportional increase in AUC at the dosage range of 1.0-4.0 mg/kg, whereas VKLE demonstrated a linear kinetics trend in general. Compared to VKI, VKLE could selectively deliver VK1 to the liver, spleen and heart. VKLE and VKI produced comparable maximal responses, in terms of coagulation factors and prothrombin time.
VKLE and VKI demonstrated different pharmacokinetics but comparable pharmacodynamics in rats.
市售维生素K1注射液（VKI）相关的严重过敏反应可能是由于添加了聚山梨酯以增溶维生素K1（VK1）所致。因此，我们试图开发不含聚山梨酯的维生素K1脂质乳剂（VKLE），以降低严重过敏反应的临床风险。本研究旨在评估VKLE与VKI在大鼠体内的药代动力学和药效学。
在大鼠中以1-4mg/kg的剂量给予VKLE或VKI后，研究VK1的血浆浓度-时间曲线。在大鼠中以2mg/kg的剂量研究VKLE和VKI的组织分布。还通过比较它们对低凝血酶原血症大鼠凝血因子（II/VII/IX/X）和凝血酶原时间的影响，研究了VKLE和VKI的药效学。
在1.0-4.0mg/kg的剂量范围内，VKI的AUC呈超比例增加，而VKLE总体上呈线性动力学趋势。与VKI相比，VKLE可以将VK1选择性地输送到肝脏、脾脏和心脏。就凝血因子和凝血酶原时间而言，VKLE和VKI产生了相当的最大反应。
VKLE和VKI在大鼠体内表现出不同的药代动力学，但药效学相当。
