Kouassi E, Caillé G, Léry L, Larivière L, Vézina M
Biopharm Drug Dispos. 1986 Jan-Feb;7(1):71-89. doi: 10.1002/bdd.2510070110.
A new gas chromatographic method was developed for the quantification of levamisole in human plasma and urine, using a nitrogen-phosphorus flame ionization detector. The adsorption of the drug onto glass was prevented by treating the glassware with a siliconizing agent. The sensitivity of the assay was 10 ng ml-1 and as low as 2 ng ml-1 can be detected in plasma. The urinary metabolite p-hydroxylevamisole was analysed by high performance liquid chromatography with ultraviolet detection. The sensitivity of this assay was 0.50 micrograms ml-1. Plasma and urinary concentrations of levamisole were determined in 10 healthy volunteers including seven men and three women following the administration of a single 150 mg dose of levamisole. Levamisole was rapidly absorbed (tmax 1.5 h), giving a peak plasma concentration of 716.7 +/- 217.5 ng ml-1. The plasma elimination half-life of levamisole was 5.6 +/- 2.5 h. Only 3.2 +/- 2.9 per cent of the oral dose was recovered as unchanged drug in the urine, suggesting the importance of clearance of levamisole by routes other than the kidney, and most probably by hepatic metabolism. The urinary concentrations of p-hydroxylevamisole were determined before and after hydrolysis of the urine samples with beta-glucuronidase, and the level of conjugation of the metabolite with glucuronic acid was then estimated. Cumulative recovery of the metabolite accounted for 1.6 +/- 1.1 per cent and 12.4 +/- 5.5 per cent of the oral dose of levamisole before and after hydrolysis, respectively, indicating that p-hydroxylation is a relatively important route of metabolism of levamisole, and that the p-hydroxylated metabolite is excreted mainly in conjugation with glucuronic acid. Except for the absorption rate of levamisole which is approximately twice as rapid in women as in men, there is no marked difference in the pharmacokinetics of levamisole between healthy men and women.
建立了一种新的气相色谱法，用于定量测定人血浆和尿液中的左旋咪唑，采用氮磷火焰离子化检测器。通过用硅烷化剂处理玻璃器皿，可防止药物吸附到玻璃上。该测定法的灵敏度为10 ng/ml，血浆中最低可检测到2 ng/ml。尿代谢物对羟基左旋咪唑采用高效液相色谱-紫外检测法进行分析。该测定法的灵敏度为0.50μg/ml。在10名健康志愿者（包括7名男性和3名女性）单次服用150 mg左旋咪唑后，测定了血浆和尿液中左旋咪唑的浓度。左旋咪唑吸收迅速（达峰时间1.5小时），血浆峰浓度为716.7±217.5 ng/ml。左旋咪唑的血浆消除半衰期为5.6±2.5小时。尿中仅回收了口服剂量3.2±2.9%的原形药物，这表明除肾脏外，左旋咪唑通过其他途径清除很重要，很可能是通过肝脏代谢。在用β-葡萄糖醛酸酶水解尿液样本前后，测定了对羟基左旋咪唑的尿浓度，然后估算了代谢物与葡萄糖醛酸的结合水平。水解前后，代谢物的累积回收率分别占左旋咪唑口服剂量的1.6±1.1%和12.4±5.5%，表明对羟基化是左旋咪唑相对重要的代谢途径，且对羟基化代谢物主要以与葡萄糖醛酸结合的形式排泄。除左旋咪唑的吸收速率女性约为男性的两倍外，健康男性和女性左旋咪唑的药代动力学无明显差异。
