Establishing individual metabolite patterns for patients on valproate therapy

• Published in: European journal of drug metabolism and pharmacokinetics 2001-01, Vol.26 (1-2), p.99-107
• Main Authors: KREHER, U, DARIUS, J, WIEN, F
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Anticonvulsants - administration & dosage; Anticonvulsants - pharmacokinetics; Anticonvulsants - therapeutic use; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Biotransformation; Child; Child, Preschool; Drug Interactions; Epilepsy - drug therapy; Epilepsy - metabolism; Female; Gas Chromatography-Mass Spectrometry; Humans; Infant; Male; Medical sciences; Neuropharmacology; Pharmacology. Drug treatments; Valproic Acid - administration & dosage; Valproic Acid - pharmacokinetics; Valproic Acid - therapeutic use
• ISSN: 0378-7966; 2107-0180
• DOI: 10.1007/BF03190383

The aim of this study was to establish individual metabolic profiles of patients receiving valproate (VPA) mono- or polytherapy in order to estimate inter- and intraindividual variability under normal conditions. Serum levels of VPA and 15 metabolites were measured by gas chromotography/mass spectrometry (GC/MS) with selected ion monitoring (SIM). Because of a huge inter-subject variability, calculating means for large epileptic populations resulted 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 changes appeared to be much less intense than inherent interindividual differences. In epileptics consecutively receiving various forms of polytherapy, alterations in the metabolic profiles occurred. Therefore, integrating different kinds of co-medication into a single polytherapy group seemed to be inadequate. 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 omega-/omega1-metabolites being strongly elevated and the major beta-metabolites (E)-2-ene and (E,E)-2,3'-diene being significantly diminished. We suggest determining the individual metabolic profile, consisting of accessible major and minor metabolites, for every patient when VPA therapy has been started or been modified. The moment any clinical complications arise, the previously obtained specific pattern of the individual can be taken as reference in order to assess the possible presance of significant alterations which might indicate or even cause any severe side effects. There seems to be no need of monitoring metabolite levels of the average patient continuously except for the high risk group (e.g. infants under 3 years age receiving polytherapy) which exhibited the highest between-subject as well as within-patient variability.