Jankovic Slobodan M, Ignjatovic Ristic Dragana
University of Kragujevac, Faculty of Medical Sciences , SvetozaraMarkovica Street, 30, 34000 Kragujevac , Serbia.
Expert Opin Drug Metab Toxicol. 2015 Mar;11(3):329-32. doi: 10.1517/17425255.2015.989211. Epub 2014 Dec 2.
Therapeutic window of anticonvulsants is not a wide one, with phenytoin being one extreme, which can be classified as a narrow therapeutic index drug, since its ratio between the least toxic and the least effective concentration is less than twofold. In order to obtain marketing authorization, a generic anticonvulsant should demonstrate relative bioequivalence with its brand-name counterpart. However, although bioequivalent, generic anticonvulsants still do not have the same bioavailability as brand-name drugs, which may lead to larger fluctuations of steady-state plasma concentrations, and sometimes to loss of seizure control if a patient is switched from brand-name to generic or from generic to generic anticonvulsant. Generic anticonvulsants are effective, safe and affordable drugs for treatment of epilepsy, and patients could be successfully treated with them from the very beginning. It is switching from brand-name to generic anticonvulsant or from one generic anticonvulsant to another that should be avoided in clinical practice, since subtle differences in bioavailability may disturb optimal degree of seizure control to which the patient was previously successfully titrated.
抗惊厥药物的治疗窗并不宽，苯妥英钠就是一个极端例子，它可被归类为治疗指数窄的药物，因为其最低中毒浓度与最低有效浓度之比小于两倍。为了获得上市许可，仿制药抗惊厥药物应证明与其品牌对应药物具有相对生物等效性。然而，尽管仿制药抗惊厥药物具有生物等效性，但它们的生物利用度仍与品牌药物不同，这可能导致稳态血浆浓度波动更大，并且如果患者从品牌药物转换为仿制药或从一种仿制药转换为另一种仿制药，有时会导致癫痫发作控制丧失。仿制药抗惊厥药物是治疗癫痫的有效、安全且经济实惠的药物，患者从一开始就可以用它们成功治疗。在临床实践中应避免从品牌药物转换为仿制药抗惊厥药物或从一种仿制药抗惊厥药物转换为另一种仿制药抗惊厥药物，因为生物利用度的细微差异可能会干扰患者先前成功滴定至的最佳癫痫发作控制程度。
