Paczkowski D, Sadowski Z, Filipek M, Koliński P
Department of Diagnostics Laboratory, Memorial Hospital-Child Health Centre, Warszawa, Poland.
Pol J Pharmacol Pharm. 1990 Jul-Aug;42(4):365-75.
Pharmacokinetics of mexiletine and its major metabolites, p-hydroxymexiletine and hydroxymethylmexiletine, were studied in 10 healthy subjects after administration of a single oral 400 mg dose. Mexiletine was extensively metabolized to hydroxymethylmexiletine and less to p-hydroxymexiletine. Mean metabolic ratio (Rm) was 0.54 and 0.18 respectively. Peak serum concentrations (Cmax) for mexiletine (0.686 +/- 0.110 micrograms/ml), hydroxymethylmexiletine (0.507 +/- 0.087 micrograms/ml), and p-hydroxymexiletine (0.096 +/- 0.046 micrograms/ml) occurred after 3.0, 4.0 and 4.2 +/- 0.6 h. Disposition parameters for mexiletine were as follows: volume of distribution (V lambda), 5.44 +/- 1.44 l/kg; serum clearance (CL) 8.08 +/- 1.23 ml/min/kg. There were no significant differences in elimination half-life (t1/2) and mean residence time (MRT) for mexiletine and its metabolites. Double-peak phenomenon was observed for all the subjects on elimination phase of mexiletine, hydroxymethylmexiletine and p-hydroxymexiletine.
在10名健康受试者口服400mg单剂量后，研究了美西律及其主要代谢产物对羟基美西律和羟甲基美西律的药代动力学。美西律广泛代谢为羟甲基美西律，较少代谢为对羟基美西律。平均代谢率（Rm）分别为0.54和0.18。美西律（0.686±0.110μg/ml）、羟甲基美西律（0.507±0.087μg/ml）和对羟基美西律（0.096±0.046μg/ml）的血清峰值浓度分别在3.0、4.0和4.2±0.6小时出现。美西律的处置参数如下：分布容积（Vλ），5.44±1.44l/kg；血清清除率（CL）8.08±1.23ml/min/kg。美西律及其代谢产物的消除半衰期（t1/2）和平均驻留时间（MRT）无显著差异。在美西律、羟甲基美西律和对羟基美西律的消除阶段，所有受试者均观察到双峰现象。
