[Status epilepticus: pharmacokinetic basis of anticonvulsant treatment in adults].
In status epilepticus, the optimal efficacy of the antiepileptic drugs depends notably on effective, quickly reached and sufficiently lasting cerebral concentrations and the optimal tolerability notably on the lack of excessive storage in the brain and other tissues. So, the best efficacy-tolerability ratio of these drugs is largely determined by their pharmacokinetic properties. A linear kinetics, a not too short distribution half-life, a neither 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 tissues are among the main ideal pharmacokinetic properties. Any of the antiepileptic drugs currently used in status epilepticus has all these properties together. An accurate knowledge of the pharmacokinetics is absolutely crucial to rationally decide the route of administration, the loading dose and the maintenance doses. However, pharmacokinetics must only complete, but cannot replace, the clinical experience and judgement, especially because some 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 during 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 the clinical efficacy and the so-called "therapeutic" plasma levels remains ill defined. The reported values are often very high and their range appears very large. Nevertheless plasma levels are useful, especially for the monitoring of the evolution; they are mandatory for nonlinear-kinetics drugs.
Broglin
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Centre Saint-Paul, hôpital Henri-Gastaut, 300, boulevard de Sainte-Marguerite, 13009 Marseille, France.
D000328:Adult; D000927:Anticonvulsants / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006801:Humans; D013226:Status Epilepticus / Q000188:drug therapy* / Q000378:metabolism
D000927:Anticonvulsants