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首页> 外文期刊>Clinical and experimental pharmacology & physiology >Pharmacokinetics of high doses of cyanocobalamin administered by intravenous injection for 26 weeks in rats.
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Pharmacokinetics of high doses of cyanocobalamin administered by intravenous injection for 26 weeks in rats.

机译：在大鼠中静脉注射高剂量的氰钴胺素，持续26周的药代动力学。

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SUMMARY 1. High doses of vitamin B(12) (cyanocobalamin) may be therapeutically effective to treat neurological alterations secondary to a wide range of disease states. The aim of the present study was to evaluate the effect of dose and repeated administration on the pharmacokinetics of cyanocobalamin in rats. 2. Forty-eight rats were randomly assigned to receive 1, 5, 25 or 100 mg/kg cyanocobalamin for 182 days (26 weeks). Cyanocobalamin plasma levels were quantified by HPLC on days 1, 85 and 182 of treatment and were analysed by means of non-compartment pharmacokinetic (PK) analysis. In addition, population PK analysis was used to fit cyanocobalamin plasma concentrations to time by means of a two-compartment model for intravascular administration. 3. The half-life of cyanocobalamin ranged from approximately 20 to 50 min, clearance ranged from 4.5 to 9 mL/min and the volume of distribution at steady state ranged from 140 to 470 mL. A statistically significant negative relationship existed between the dose of cyanocobalamin and the normalized area under the plasma concentration-time curve (AUC). This non-linearity was not exhibited in population PK analysis. No evidence of toxicity was observed. 4. At very high and prolonged doses (up to 100 mg/kg for 26 weeks), intravascular administration of cyanocobalamin in rats follows a two-compartment kinetic model and cyanocobalamin undergoes extensive extravascular distribution. The negative relationship between dose and normalized AUC is compatible with possible saturation of tubular reabsorption, thus increasing renal clearance at higher doses.
机译：概述1.高剂量的维生素B（12）（氰基巴巴马星）可能有效治疗继发于多种疾病状态的神经系统改变。本研究的目的是评估剂量和重复给药对氰钴胺素在大鼠体内药代动力学的影响。 2. 48只大鼠随机分为182天（26周）接受1、5、25或100 mg / kg氰钴胺素。在治疗的第1、85和182天通过HPLC定量氰钴胺血浆水平，并通过非房室药代动力学（PK）分析进行分析。另外，通过两室模型用于血管内施用，使用群体PK分析来使氰钴胺素血浆浓度适应时间。 3.氰钴胺素的半衰期为约20至50分钟，清除率为4.5至9 mL / min，稳态时的分布体积为140至470 mL。在血浆浓度-时间曲线（AUC）下，氰钴胺的剂量与标准化面积之间存在统计学上的显着负相关。这种非线性在种群PK分析中没有表现出来。没有观察到毒性的证据。 4.在非常高的剂量和延长的剂量下（长达26周，最高剂量为100 mg / kg），大鼠腔内施用氰钴胺素遵循两室动力学模型，氰钴胺素在血管内分布广泛。剂量与标准化AUC之间的负相关关系可能与肾小管重吸收的饱和有关，因此在较高剂量下可增加肾脏清除率。

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