Status epilepticus: pharmacokinetic basis of the antiepileptic therapy in adults.

In status epilepticus, the optimal efficacy of the antiepileptic drugs depe nds notably on effective, quickly reached and sufficiently lasting cerebral concentrations and the optimal tolerability notably on the lack of excessi ve storage in the brain and other tissues. So, the best efficacy-tolerabili ty ratio of these drugs is largely determined by their pharmacokinetic prop erties. A linear kinetics, a not too short distribution half-life, a neithe r too brief nor too long elimination half-life, a fast and easy crossing of the blood-brain barrier and the lack of long-lasting accumulation in fat t issues are among the main ideal pharmacokinetic properties. Any of the anti epileptic drugs currently used in status epilepticus has all these properti es together. An accurate knowledge of the pharmacokinetics is absolutely cr ucial to rationally decide the route of administration, the loading dose an d the maintenance doses. However, pharmacokinetics must only complete, but cannot replace, the clinical experience and judgement, especially because s ome limitations: kinetic equations are mathematically exact but theoretical ; individual kinetics in a given patient is exceptionally known in clinical practice; finally the pharmacokinetics may be significantly modified durin g a status epilepticus, especially of the generalized convulsive type, due to systemic consequences and complications of the seizures. In the emergency situation of status epilepticus, the correlation between t he clinical efficacy and the so-called "therapeutic" plasma levels remains ill defined. The reported values are often very high and their range appear s very large. Nevertheless plasma levels are useful, especially for the mon itoring of the evolution; they are mandatory for nonlinear-kinetics drugs. (C) 2001 Editions scientifiques et medicales Elsevier SAS.