Establishing individual metabolite patterns for patients on valproate therapy

The aim of this study was to establish individual metabolic profiles of pat ients receiving valproate (VPA) mono- or polytherapy in order to estimate i nter- and intraindividual variability under normal conditions. Serum levels of VPA and 15 metabolites were measured by gas chromotography/mass spectro metry (GC/MS) with selected ion monitoring (SIM). Because of a huge inter-s ubject variability, calculating means for large epileptic populations resul ted in broad and vague ranges for serum levels of VPA and its metabolites. It therefore remained difficult to recognize any significant alteration in the individual metabolic profile. Over long term periods, within-patient ch anges appeared to be much less intense than inherent interindividual differ ences. In epileptics consecutively receiving various forms of polytherapy, alterations in the metabolic profiles occurred. Therefore, integrating diff erent kinds of ca-medication into a single polytherapy group seemed to be i nadequate. An adult patient on VPA monotherapy, suffering form intrahepatic metastasis and renal insufficiency, showed an extremely altered metabolic pattern, with the 4-ene and the omegaw-/omega1-metabolites being strongly e levated and the major a-metabolites (E)-2-ene and (E,E)-2,3'-diene being si gnificantly diminished. We suggest determining the individual metabolic pro file, consisting of accessible major and minor metabolites, for every patie nt when VPA therapy has been started or been modified. The moment any clini cal complications arise, the previously obtained specific pattern of the in dividual can be taken as reference in order to assess the possible presance of significant alterations which might indicate or even cause any severe s ide effects. There seems to be no need of monitoring metabolite levels of t he average patient continuously except for the high risk group (e.g. infant s under 3 years age receiving polytherapy) which exhibited the highest betw een-subject as well as within-patient variability.