Maurer T S, Mishra Y, Fung H L
Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, Buffalo, NY 14260-1200, USA.
Biopharm Drug Dispos. 1999 Nov;20(8):397-400. doi: 10.1002/1099-081x(199911)20:8<397::aid-bdd196>3.0.co;2-m.
L-N(G)-methyl-arginine (L-NMMA) is an inhibitor of nitric oxide synthase (NOS) enzymes. We have characterized the pharmacokinetics of L-NMMA in rats using HPLC. The HPLC assay requires pre-column derivatization, gradient elution and ultraviolet detection. The limit of sensitivity in plasma was 3.0 microM (0.75 microg mL(-1)). Using this assay, the pharmacokinetics of L-NMMA were characterized following iv bolus doses of 25, 50 and 100 mg kg(-1). Compartmental and noncompartmental data analysis suggest that L-NMMA pharmacokinetics are nonlinear at these doses. From the nonlinear compartmental analysis, we estimated the K(m) and V(max) parameters of L-NMMA elimination to be 70.2 microM and 4.59 microM min(-1), respectively. This estimated K(m) value of L-NMMA elimination is consistent with its nonlinear elimination characteristics in humans and its saturable metabolism by the N(G), N(G)-dimethylarginine dimethylamino-hydrolase enzyme in isolated rat tissue.
L-N（G）-甲基精氨酸（L-NMMA）是一氧化氮合酶（NOS）的抑制剂。我们利用高效液相色谱法（HPLC）对大鼠体内L-NMMA的药代动力学进行了表征。HPLC分析需要柱前衍生化、梯度洗脱和紫外检测。血浆中的灵敏度极限为3.0微摩尔/升（0.75微克/毫升）。采用该分析方法，在静脉注射25、50和100毫克/千克的剂量后，对L-NMMA的药代动力学进行了表征。房室和非房室数据分析表明，在这些剂量下L-NMMA的药代动力学是非线性的。通过非线性房室分析，我们估计L-NMMA消除的米氏常数（K(m)）和最大反应速度（V(max)）参数分别为70.2微摩尔/升和4.59微摩尔/分钟。L-NMMA消除的这一估计K(m)值与其在人体内的非线性消除特征以及在离体大鼠组织中被N（G），N（G）-二甲基精氨酸二甲氨基水解酶的饱和代谢相一致。
