Richens A
Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Cardiff, UK.
J Child Neurol. 1991;Suppl 2:S7-10.
Vigabatrin is an enzyme-activated, irreversible inhibitor of gamma-aminobutyric acid (GABA) aminotransferase, which causes a marked increase in cerebral GABA concentration and a resulting anticonvulsant action. Recovery from its effects requires the synthesis of new enzyme, and this may take several days following a single dose. The pharmacokinetics of vigabatrin are not a good guide to its duration of action. It is cleared rapidly by renal elimination (giving a plasma half-life of approximately 7 to 9 hours), and therefore the effect of the drug long outlasts its presence in the body. Plasma drug level monitoring is therefore of little value in regulating vigabatrin therapy. The drug is not bound to plasma proteins. Interactions with other drugs would not be expected because of its predominant renal elimination and its lack of protein binding. Also, vigabatrin does not induce liver enzymes, as do many of the standard antiepileptic drugs. In several trials, however, a small but significant reduction in phenytoin levels has been seen following the addition of vigabatrin to the antiepileptic medication. The mechanism for this reduction in phenytoin levels has not yet been elucidated, though it does not appear to be of clinical significance.
氨己烯酸是一种酶激活的、不可逆的γ-氨基丁酸（GABA）转氨酶抑制剂，可使脑内GABA浓度显著升高，从而产生抗惊厥作用。从其作用中恢复需要合成新的酶，单次给药后这可能需要数天时间。氨己烯酸的药代动力学并不能很好地指导其作用持续时间。它通过肾脏排泄迅速清除（血浆半衰期约为7至9小时），因此药物的作用在其在体内消失后仍会持续很长时间。因此，血浆药物水平监测在调整氨己烯酸治疗中价值不大。该药物不与血浆蛋白结合。由于其主要通过肾脏排泄且缺乏蛋白结合，预计不会与其他药物发生相互作用。此外，氨己烯酸不像许多标准抗癫痫药物那样诱导肝酶。然而，在几项试验中，在抗癫痫药物中添加氨己烯酸后，苯妥英水平出现了小幅但显著的降低。尽管这种苯妥英水平降低的机制尚未阐明，但似乎不具有临床意义。
