Clinical pharmacokinetics of newer antiepileptic drugs. Lamotrigine, vigabatrin, gabapentin and oxcarbazepine.

Abstract

The clinical pharmacokinetics of the 4 antiepileptic drugs lamotrigine, vigabatrin, gabapentin and oxcarbazepine have been reviewed in this paper. All the drugs have linear kinetics and reliable absorption, although the saturation of transport across the gut may occur at high doses with gabapentin. All the drugs can be conveniently given as a twice daily dosage apart from gabapentin, which has a short half-life and a midday dose is needed. Unlike many of the older drugs, lamotrigine, vigabatrin and gabapentin have a predominantly renal excretion and are not metabolised through the cytochrome P450 system. They do not induce their own metabolism or that of other commonly used anticonvulsants. Similarly, clinically important interactions with other major classes of drugs metabolised this way, such as anticoagulants or steroid hormones, do not occur. Oxcarbazepine, however, can cause oral contraceptive pill failure. Oxcarbazepine is immediately metabolised to a hydroxy metabolite and could be considered a prodrug. It appears to have fewer pharmacokinetic interactions than carbamazepine. Valproic acid (sodium valproate) inhibits the glucuronidation of lamotrigine and increases its half-life; when used together, dosage modification of lamotrigine is needed to avoid toxicity.