Hirata Kenshiro, Saruwatari Junji, Enoki Yuhuki, Iwata Kazufumi, Urata Yukino, Aizawa Keiji, Ueda Kentaro, Shirouzono Takumi, Imamura Motoki, Moriuchi Hiroshi, Ishima Yu, Kadowaki Daisuke, Watanabe Hiroshi, Hirata Sumio, Maruyama Toru, Fukunaga Eiko
*Department of Pharmacy, Japanese Red Cross Kumamoto Hospital; †Division of Pharmacology and Therapeutics; ‡Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University; §Department of Clinical Pharmacy, Faculty of Pharmaceutical Science, Sojo University; ¶Center for Clinical Pharmaceutical Sciences; and ‖Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Ther Drug Monit. 2014 Oct;36(5):553-5. doi: 10.1097/FTD.0000000000000067.
: In this report, the authors described the unusual case of a patient in whom the plasma phenytoin concentration was unexpectedly not detected on a particle-enhanced turbidimetric inhibition immunoassay (PETINIA) technique, a typical immunoassay for phenytoin. The plasma concentration was measured using PETINIA and high-performance liquid chromatography in a 69-year-old male patient treated with fosphenytoin intravenously at the standard dose for 7 days. Although the plasma concentration of phenytoin was below the limit of detection (<0.5 mcg/mL) on PETINIA after the administration of fosphenytoin, the trough plasma concentration was estimated to be between 5 and 10 mg/L on high-performance liquid chromatography. When the plasma concentrations of IgM and IgG were measured using an enzyme-linked immunosorbent assay, the plasma IgG level was within the reference range, whereas the plasma IgM level was 2-3 times higher than the upper limit of the reference range. We concluded that the PETINIA method yielded a possible false-negative result regarding the phenytoin level in this patient, perhaps because of some hindrance to the measurement process by IgM. This case suggests that false-negative results should be considered when therapeutic drug monitoring reveals abnormally low values using PETINIA and that it is necessary to evaluate the plasma IgM level.
在本报告中，作者描述了一例不寻常的病例。在一名69岁男性患者中，使用苯妥英典型的免疫测定方法——颗粒增强比浊抑制免疫测定法（PETINIA）意外未检测到血浆苯妥英浓度。该患者以标准剂量静脉注射磷苯妥英7天，使用PETINIA和高效液相色谱法测量其血浆浓度。尽管在给予磷苯妥英后，PETINIA检测到的苯妥英血浆浓度低于检测限（<0.5 mcg/mL），但高效液相色谱法测得的谷浓度估计在5至10 mg/L之间。当使用酶联免疫吸附测定法测量IgM和IgG的血浆浓度时，血浆IgG水平在参考范围内，而血浆IgM水平比参考范围上限高2至3倍。我们得出结论，PETINIA方法在该患者的苯妥英水平上可能产生了假阴性结果，这可能是由于IgM对测量过程造成了某种阻碍。该病例表明，当治疗药物监测使用PETINIA显示异常低值时，应考虑假阴性结果，并且有必要评估血浆IgM水平。
