Yamasaki S, Sakurai E, Hikichi N, Sakai N, Maeyama K, Watanabe T
Department of Pharmaceutics I, Tohoku College of Pharmacy, Sendai, Japan.
J Pharm Pharmacol. 1994 May;46(5):371-4. doi: 10.1111/j.2042-7158.1994.tb03815.x.
Using a modified HPLC method with a fluorescence spectrophotometer and a weak cation exchanger, it was possible to separate (R)-alpha-methylhistamine (alpha-methylhistamine) from histamine in plasma and various tissues. The assay was used to study the disposition and pharmacokinetic analysis of alpha-methylhistamine after a bolus intravenous administration to rats. After rapid intravenous administration (12.6 mg kg-1), the plasma concentration declined biexponentially with a half-life of 1.3 min in the elimination phase. The area under the plasma concentration-time curve and total body clearance were 130 micrograms min mL-1 and 97 mL min-1 kg-1, respectively. After administration, alpha-methylhistamine was immediately transferred to various tissues. The concentration was high in the kidney, lung, and liver (kidney > lung > liver), but low in the brain. The tissue-to-plasma concentration ratios in peripheral tissues were greater than 1, suggesting that the transfer of alpha-methylhistamine to peripheral tissues was due to a specialized transport mechanism or possibly to tissue binding. However, the finding that the tissue/plasma ratio in the brain was lower than unity suggests that the transport system in this tissue depends on a concentration gradient, and that alpha-methylhistamine crosses the blood-brain barrier in rats with difficulty.
使用配备荧光分光光度计和弱阳离子交换剂的改良高效液相色谱法，能够从血浆和各种组织中的组胺中分离出（R）-α-甲基组胺（α-甲基组胺）。该测定法用于研究大鼠静脉推注给药后α-甲基组胺的处置和药代动力学分析。快速静脉给药（12.6 mg·kg⁻¹）后，血浆浓度在消除期呈双指数下降，半衰期为1.3分钟。血浆浓度-时间曲线下面积和全身清除率分别为130μg·min·mL⁻¹和97 mL·min⁻¹·kg⁻¹。给药后，α-甲基组胺立即转移到各种组织中。在肾脏、肺和肝脏中的浓度较高（肾脏＞肺＞肝脏），但在脑中浓度较低。外周组织中的组织-血浆浓度比大于1，表明α-甲基组胺向外周组织的转移是由于一种特殊的转运机制或可能是由于组织结合。然而，脑中组织/血浆比低于1的发现表明，该组织中的转运系统取决于浓度梯度，并且α-甲基组胺在大鼠中难以穿过血脑屏障。
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