Implementation of a novel immunoassay for the determination of lamotrigine in human serum and its impact on clinical practice

• Autores: Oscar Pascual Marmaneu, M. Dolores Bellés Medall, M. Mendoza Aguilera, Tamara Álvarez Martín, Celia Raga Jiménez, Raúl Ferrando Piqueres
• Localización: European journal of clinical pharmacy: atención farmacéutica, ISSN 2385-409X, Vol. 20, Nº. 3, 2018, págs. 4-4
• Idioma: inglés
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• Resumen

  • Background: Recently, the ARK® enzyme immunoassay has been implemented in Architect c4000® analyzer for automated therapeutic drug monitoring of serum concentrations of lamotrigine.

    Objective: To verify the performance of this enzyme immunoassay, analyze the impact of automation on the follow-up of patients treated with lamotrigine and detect subpopulations that get most benefit from therapeutic drug monitoring of lamotrigine.

    Method: Samples of lamotrigine were analyzed first by HPLC (gold standard method) and second by Architect c4000®, and the linearity and concordance between both methods was evaluated. Afterwards, a retrospective observational study that included serum samples of lamotrigine of 24 months was conducted. The influence of the variables (age, sex, pregnancy, co-administration with valproic acid and glucuronidation inducing drugs) in lamotrigine apparent oral clearance (CLp/F) was evaluated by a multivariate linear regression.

    Results: 85 samples were measured by both methods; linearity was good according to CUSUM test (P >0.2). The agreement was low according to result Lin's coefficient of 0.442. After enzyme immunoassay implantation, a 62.9% and 47.5% increase of lamotrigine determinations and patients monitored was observed. The median of Clp/F was higher (p <0.05) in pregnancy (12.6 L/h; IQR: 9.4-26.2) and in association with UGT inducers (8.1 L/h; IQR: 5.2-11.4) and lower (p <0.05) in the co-administration with valproic (1.8 L/h; IQR: 1.5-2). In the pregnant women, a 240% increase in Clp/F was observed in relation to the pre-gestation situation.

    The acceptance of the therapeutic drug monitoring report was 89% in pregnancy, 74% in co-administration with valproic, 56% without cofactors and 36% in association with inducers.

    Conclusions: the incorporation of the automated enzyme immunoassay method into clinical practice required the correction of the result obtained. In the concomitant administration with valproic acid and during pregnancy, close monitoring of lamotrigine concentrations must be carried out