メキシレチンの血中濃度の検討

Abstract

As the therapeutically effective blood level of mexiletine (MX), a recently marketed antiarrhythmic agent, is narrow at 0.5-2.0μg/ ml, the side-effect occurrence rate increases when the blood level of the drug exceeds 2.0μg/ ml. Therefore, close monitoring of the blood level of the drug is required after administration of the drug.We developed a new method for this measurement using high-performance liquid chromatography (HPLC), which is more convenient than the previous method by gas chromatography. The general procedure is as follows: An internal standard (4-methylmexiletine) is added to the serum sample, followed by the addition of a sodium hydroxide solution, and the whole is mixed well, then injected into an extrelut (manufactured by Merck Co.). The mixture is extracted with diethyl ether, and the extract is evaporated to dryness, and dissolved in an elution solvent, then subjected to the HPLC analysis.The values obtained by the peak-height method showed a lineality at 0.2-5.0μg/ ml. The recovery rate from the serum, to which MX was added at 2.5μg/ ml, was 80.4-90.0%. Coefficient validity was 3.1%. Good chromatographic data was also obtained in measurement of serum levels in patients administered MX.