Parant François, Moulsma Mustapha, Gagnieu Marie Claude, Lardet Gisèle
UF 21 303, Pharmacologie et Toxicologie Analytique, Analyses des Eléments Trace, Fédération de Biochimie, Hôpital Edouard Herriot, Lyon, France.
Ther Drug Monit. 2005 Aug;27(4):457-62. doi: 10.1097/01.ftd.0000160718.88822.20.
A 32-year-old epileptic patient with a lengthy history of multiple-drug abuse and psychotic disorders was found to have an elevated serum carbamazepine concentration of 40.5 mg/L (therapeutic range 4-12 mg/L) using particle-enhanced turbidimetric inhibition immunoassay (PETINIA). Serum reanalysis by LC-DAD revealed only high hydroxyzine (HDZ) concentration (HDZ = 0.55 mg/L; therapeutic range <0.1 mg/L), suggesting cross-reactivity between HDZ and PETINIA. To confirm this hypothesis, the authors tested 2 commercially available carbamazepine immunoassays, PETINIA and EMIT 2000, for in vitro cross-reactivity with HDZ and 2 HDZ metabolites (cetirizine and norchlorcyclizine). To determine the frequency of this interaction in a clinical setting, 40 sera of 39 patients taking HDZ without carbamazepine were tested by both immunoassays. For some samples, LC-ESI-MS analysis of HDZ metabolites was performed. Additionally, cross-reactivities produced by other benzhydrylpiperazine drugs were evaluated. in vitro, 5 mg of HDZ, cetirizine, and norchlorcyclizine cross-reacted with PETINIA at 85%, 125%, and 66%, respectively. Conversely, EMIT 2000 showed no cross-reactivity. For PETINIA, erroneous carbamazepine concentrations were detected in 35 out of 40 sera of patients taking HDZ. The magnitude of interference correlated moderately with serum HDZ concentrations (Spearman rho coefficient 0.58, P < 0.001), suggesting a major role for the multiple HDZ metabolites (4 serum metabolites were detected by LC-ESI-MS). Furthermore, other benzhydrylpiperazine drugs (eg, oxatomide) showed in vitro cross-reactivity with PETINIA. In conclusion, HDZ and its metabolites cross-react with carbamazepine PETINIA immunoassay, which could significantly affect the correct interpretation of serum carbamazepine concentrations in patients treated with HDZ.
一名32岁有长期多种药物滥用和精神疾病史的癫痫患者，采用颗粒增强比浊抑制免疫测定法（PETINIA）检测发现其血清卡马西平浓度升高至40.5mg/L（治疗范围为4 - 12mg/L）。通过液相色谱 - 二极管阵列检测（LC - DAD）对血清进行重新分析，结果显示仅羟嗪（HDZ）浓度较高（HDZ = 0.55mg/L；治疗范围<0.1mg/L），提示HDZ与PETINIA之间存在交叉反应。为证实这一假设，作者测试了2种市售的卡马西平免疫测定法，即PETINIA和EMIT 2000，检测它们与HDZ及其2种HDZ代谢产物（西替利嗪和去氯环嗪）的体外交叉反应性。为确定在临床环境中这种相互作用的频率，对39名服用HDZ但未服用卡马西平的患者的40份血清进行了这两种免疫测定法检测。对于一些样本，进行了HDZ代谢产物的液相色谱 - 电喷雾电离质谱（LC - ESI - MS）分析。此外，还评估了其他二苯甲基哌嗪类药物产生的交叉反应性。在体外，5mg的HDZ、西替利嗪和去氯环嗪与PETINIA的交叉反应率分别为85%、125%和66%。相反，EMIT 2000未显示交叉反应性。对于PETINIA，在服用HDZ的患者的40份血清中，有35份检测到错误的卡马西平浓度。干扰程度与血清HDZ浓度呈中度相关（斯皮尔曼相关系数0.58，P < 0.001），提示多种HDZ代谢产物起主要作用（通过LC - ESI - MS检测到4种血清代谢产物）。此外，其他二苯甲基哌嗪类药物（如奥沙米特）在体外与PETINIA显示交叉反应性。总之，HDZ及其代谢产物与卡马西平PETINIA免疫测定法发生交叉反应，这可能会显著影响接受HDZ治疗患者血清卡马西平浓度的正确解读。
