Hagstrom J N, Bovill E G, Soll R F, Davidson K W, Sadowski J A
Department of Pathology, University of Vermont, Burlington 05405-0068, USA.
Thromb Haemost. 1995 Dec;74(6):1486-90.
Prenatal maternal vitamin K1 supplementation to improve the hemostatic status of the fetus may depend upon the route of administration and subsequent presentation at the placental barrier. We investigated intramuscular (IM) vs oral (PO) vitamin K1 supplementation in eight healthy, nonpregnant women of childbearing age. Pharmacokinetics were studied in each subject after a 5 mg IM dose and after a 5 mg oral dose of vitamin K1 approximately one month later. Plasma collected at the peak vitamin K level for each treatment was separated into very low density lipoproteins (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL) and lipoprotein-free fractions by density gradient ultracentrifugation. Vitamin K1 was measured in the plasma and lipoprotein fractions using HPLC. The concentration of vitamin K1 in plasma reached a peak 2 h after an IM dose and remained high throughout the 30 h course of the study. In contrast, the oral dose of vitamin K1 peaked at 4 h and rapidly decreased to near baseline by 18 to 30 h. The distribution of vitamin K1 in the lipid fractions was different for IM compared to PO. The percentage of vitamin K1 in the VLDL fraction at the peak for an oral dose was significantly higher than for an IM dose (80.8% +/- 3.5 vs 10.8% +/- 6.5, p < 0.0001). After the oral absorption stage, the subjects took 5 mg of vitamin K1 orally, once a day, for 12 days. No significant differences were observed for the following coagulation proteins and hemostatic markers measured immediately before and after long-term oral vitamin K supplementation: factor II, factor VII, protein C, and thrombin-antithrombin III complex. In conclusion, physiological processing of supplemented vitamin K1 differs in the IM vs PO routes of administration and 12 days of oral vitamin K1 does not alter the concentration of selected vitamin K-dependent coagulation proteins or thrombin-antithrombin complex generation.
产前母体补充维生素K1以改善胎儿的止血状态可能取决于给药途径以及随后在胎盘屏障处的呈现情况。我们在八名健康的育龄非孕妇中研究了肌肉注射（IM）与口服（PO）维生素K1补充剂的情况。在每名受试者接受5毫克肌肉注射剂量的维生素K1后，约一个月后再接受5毫克口服剂量的维生素K1，之后对其进行药代动力学研究。在每种治疗的维生素K水平达到峰值时采集的血浆通过密度梯度超速离心法分离为极低密度脂蛋白（VLDL）、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）和无脂蛋白部分。使用高效液相色谱法（HPLC）测量血浆和脂蛋白部分中的维生素K1。肌肉注射剂量后2小时血浆中维生素K1浓度达到峰值，并在整个30小时的研究过程中保持较高水平。相比之下，口服维生素K1剂量在4小时达到峰值，并在18至30小时迅速降至接近基线水平。与口服相比，肌肉注射时维生素K1在脂质部分的分布有所不同。口服剂量峰值时VLDL部分中维生素K1的百分比显著高于肌肉注射剂量（80.8%±3.5对10.8%±6.5，p<0.0001）。在口服吸收阶段后，受试者每天口服5毫克维生素K1，持续12天。在长期口服维生素K补充前后立即测量的以下凝血蛋白和止血标志物未观察到显著差异：凝血因子II、凝血因子VII、蛋白C和凝血酶 - 抗凝血酶III复合物。总之，补充的维生素K1在肌肉注射与口服给药途径中的生理处理方式不同，并且口服12天维生素K1不会改变所选维生素K依赖凝血蛋白的浓度或凝血酶 - 抗凝血酶复合物的生成。
