Pharmacokinetic and Placental Transfer of Levetiracetam

Hypotheses: The treatment of epilepsy during pregnancy is difficult because of the risk of anti-epileptic drugs on the one hand and the risk of destabilization of epilepsy in the mother on the other hand. There is limited data on the pharmacokinetics (concentration study) and pharmacodynamics (efficacy and toxicity effects study) of levetiracetam in pregnant women. The few studies focus on few women and show very strong interindividual variability and a tendency to decrease total concentrations.

Main objective: To develop a population pharmacokinetic model of levetiracetam during pregnancy. After the study, this model could be used to propose dose adjustments to maintain stable concentrations in pregnant women throughout pregnancy.

Secondary objectives:

* Describe placental transfer during childbirth and during a medical termination of pregnancy
* Link the concentration and its variation in the individual to the effects of treatment

Methodology: Are included by the neurology service, pregnant women which are already under levetiracetam and / or obstetric gynecology services for her treatment of epilepsy, pregnant women at first consultation. Women are already taking levetiracetam and the drug is not provided by the study40 mother-child couples, as well as 10 women who undergo a medical termination of pregnancy will have to be included in the study, in 7 maternities in Paris.

Women are already taking the drugs, according to the practices of the different services, and the study will not change their prescriptions of these drugs. The women will have a blood sample at 3 visits during pregnancy (11-14 weeks, 24-28 weeks and 35-39 weeks) and at the post-partum consultation. At delivery, a collection of the mother, cord blood and amniotic fluid will be performed. A salivary specimen will be routinely collected at the same time as the mother's plasma sample.

The pharmaco-statistical analysis will be conducted using non-linear mixed-effect modeling programs (Monolix and Nonmem) to calculate the main pharmacokinetic parameters of the mother and fetus and to estimate their variability. This type of modeling makes it possible to take into account individual covariates (weight, gestational age ...) to explain the pharmacokinetic variability between mother - child pairs. The final model will be validated by a simulation technique. The final model will be used to rationalize the changes in antiepileptic doses during pregnancy and to explain the differences in passage, based on individual covariates, then to perform simulations to find out how to modify the administration for treatment to be effective as often as possible.

The secondary endpoints are

* Exposure ratio (area under the concentration-time curve) between the mother and the fetus to describe the transplacental passage of levetiracetam levetiracetam.
* To correlate the evolution of the concentrations in the woman (value in the woman whose treatment is balanced before the pregnancy minus the value when she is pregnant) to

  * the effectiveness (number of crises that the patient did).
  * tolerance: presence or absence of clinical and biological abnormalities occurring in pregnant women and children

Eligibility Criteria:
Inclusion Criteria:

* pregnant Women of childbearing age who are pregnant
* Age ≥18 years
* Women with epilepsy treated with levetiracetam in monotherapy or combination
* affiliated to a social security scheme (or entitled)

Exclusion Criteria:

* Women treated with antiepileptics for pathology other than epilepsy
* Women treated with a combination of more than 3 antiepileptics
* Severe anemia
* Renal failure (moderate to severe)
* Hepatic impairment (moderate to severe)
* Alcohol and/or recreational drug use
* Trend towards non-compliance with treatment
* Inability to maintain a Crisis Observation Workbook
* Suicidal Ideas
* Uncontrolled thyroid disease