Abstract1,2‐ and 1,3‐glyceryl dinitrates (1,2‐GDN and 1,3‐GDN) are the primary metabolites of glyceryl trinitrate, a commonly used anti‐anginal agent. The goal of this study was to examine the pharmacokinetic properties of these metabolites in rats. Sprague‐Dawley rats were infused intravenously with 0·25 or 2·0 μgmin−1of either 1,2‐ or 1,3‐GDN for 70 min, during which steady state blood concentrations were achieved. Post‐infusion blood samples were collected for 30 min. 1,2‐GDN was found to possess slightly higher clearance (32·3 vs 21·8 ml min−1kg−1) and volume of distribution (695 vs 454 ml kg−1) than 1,3‐GDN; however, the two metabolites exhibited similar mean residence times (22·0 vs 21·8 min). Upon an 8‐fold increase in the infusion rate, the pharmacokinetic parameters were not significantly altered for either 1,2‐ or 1,3‐GDN. When each GDN was co‐infused with an 8‐fold higher dose of the other GDN, there were
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机译:摘要1,2-和1,3-甘油二硝酸酯(1,2-GDN和1,3-GDN)是常用的抗心绞痛剂三硝酸甘油的主要代谢产物。本研究的目的是检查这些代谢物在大鼠中的药代动力学特性。Sprague-Dawley大鼠静脉注射0.25或2.0μgmin-1的1,2-或1,3-GDN70分钟,在此期间达到稳态血药浓度。收集输注后血样 30 分钟,发现 1,2-GDN 的清除率(32·3 vs 21·8 ml min-1kg-1)和分布体积(695 vs 454 ml kg-1)略高于 1,3-GDN;然而,两种代谢物表现出相似的平均停留时间(22·0 vs 21·8 min)。输注速率增加 8 倍后,1,2-或 1,3-GDN 的药代动力学参数均未发生显着变化。当每个 GDN 与另一个 GDN 的 8 倍高剂量共同输注时,有
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