Elimination of anti-epileptic compounds in Marseille aquatic environment from private hospital effluent - modelling versus measurements
C.Crepin(1), E.Fuseau(1), M.Portugal(2), D.Humilier(2)
(1) EMF consulting, Aix en Provence (2) HŰpital Henri Gastaut, Marseille,Introduction: European directives require that residues of drug found in the aquatic environment should be taken account for a new drug application submission. .
A lot of anti-epileptic drugs (AED) are used to reduce the number of seizures in patients (children, adolescents and adults) with epilepsy. The metabolism of each AED is influenced by concurrent anti-epileptic medication. Carbamazepine, second generation of AED was recognised as a compound that is not affected by conventional sewage treatment and that is also highly persistent in the aquatic environment. 
Objectives: The objectives are to predict the load of two AEDs (valproate (VAL) and carbamazepine (CAR)), originating from hospital in Marseille in the sewer system and the receiving sewage treatment plants (STPs) using AED PK excretion model and to compare these results with actual measurements of AED concentrations collected from the hospital effluents and from general Marseille sewage.
Methods: The population used is a database including the number of patients treated in the Henri Gastaut hospital in Marseille during one year. Only patients (children, adolescents, adults) receiving carbamazepine and /or valproate are considered.
Using the relevant population PK models and the exposed population, Monte Carlo simulations of exposure and excretion are performed with NONMEM. Concentrations of AEDs in the hospital effluents will be extrapolated over one year and compared to actual measurements in Henri Gastaut hospital.
 EMEA/CHMP/SWP/4447/00, Guideline on the environmental risk assessment of medicinal products for human use (2006)
 Thomas Heberer, Dirk Feldmann, Contribution of effluents from hospitals and private households to the total loads of diclofenac and carbamazepine in municipal sewage effluents-modelling versus measurements, Journal of hazardous Materials 122 (2005) 211-218