STUDY REGARDING THE DETERMINATION OF VALPROIC ACID SERUM LEVELS BY EMIT
MIHAIL SILVIU TUDOSIE 1#, GENICA CARAGEA 2, ILEANA DANESCU 2, CATALIN-GABRIEL SMARANDACHE 1#, ANA MARIA DASCALU 1#, ANDREEA-MARIA SMARANDACHE 1, BOGDAN SOCEA 1, DRAGOS MARIAN POPESCU 3, SILVIU MIREL PITURU 1, RADU VIRGIL COSTEA 1*, RADU MACOVEI 1,2, DRAGOS SERBAN 1
1.“Carol Davila” University of Medicine and Pharmacy Bucharest, Romania
2.Intensive Care Unit of the Emergencies Clinical Hospital Bucharest, Romania
3.University of Medicine and Pharmacy Craiova, Romania
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Valproic acid (n-dipropylacetic acid) is a unique anticonvulsant due to its structure, used in treating anxiety, alcoholism and mood disorders. At therapeutic doses, valproic acid half-life varies from 10 to 20 hours in adults, while it is significantly shorter (6 to 9 hours) in children. It is metabolized at hepatic level into several metabolites of which two in larger quantities, namely 2-en-VPA (2-propyl-2-pentenoic acid) and 3-keto VPA (2-propyl-3-keto-pentanoic acid) which form as a result of a beta hepatic microsomal oxidation. These two metabolites can be identified in urine in proportion of 70%. In case of an overdose or of long-term treatment, high serum levels of hepatic enzymes and hyperammonaemia may appear. A less frequent side effect is acute pancreatitis, with high serum amylase. The plasma concentration of VPA higher than 100 mg/L is concerning and a concentration higher than 450 mg/L is associated with a moderate or severe prognostic, although there is no tight correlation between plasma levels of VPA and the severity of clinical signs. Immunochemical methods use a specific antibody for the tested molecule and a marked form of the same compounds. There are two main ways to quantify the reaction: homogenous phase method and heterogeneous phase method. The homogenous methods, faster and completely automized are: EMIT (Enzyme Multiplied Immunoassay Technique) and FPIA (Fluorescence Polarization Immunoassay Technique). In the EMIT method, the marking is made through an enzyme by binding the antibody to the labelled enzyme molecule and this method can be applied confidently to determine the serum levels of valproic acid. Also, it is useful both in monitoring valproic acid treatment and, especially, in establishing a certain diagnosis in acute mono or multidrug acute intoxications.
