期刊
THERAPEUTIC DRUG MONITORING
卷 36, 期 4, 页码 494-498出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FTD.0000000000000051
关键词
antiepileptic drugs; pharmacokinetic interactions; lacosamide; enzyme-inducing antiepileptic drugs; therapeutic drug monitoring; serum lacosamide concentration
资金
- National Institute for Health Research University College London Hospitals Biomedical Research Centre
- National Institute for Health Research [NF-SI-0509-10161] Funding Source: researchfish
Objective: Lacosamide (LCM), a new antiepileptic drug (AED) approved as adjunctive therapy for the treatment of patients with partial-onset seizures, has limited pharmacokinetic and drug interaction data. The main objectives of the present study were to investigate the effects of dose, age, gender, and hepatic enzyme-inducing AEDs on the pharmacokinetics of LCM as assessed by steady state serum LCM values. Methods: An LCM AED therapeutic drug monitoring database was analyzed with regard to LCM serum concentrations and other relevant patient and AED drug information. One hundred twenty eight sera were identified. These were collected from 68 women and 61 men aged 19-66 years, who were prescribed a median LCM dose of 300 mg (range 50-600 mg). Results: Serum LCM concentrations were observed in the following main groupings: LCM monotherapy (n = 5), LCM with nonenzyme-inducing AEDs (n = 50), LCM with enzyme-inducing AEDs (n = 49), LCM with valproic acid (n = 20), and LCM with enzyme-inducing AEDs plus valproic acid (n = 4). Analysis of variance showed a correlation of dose with LCM concentrations (r = 0.53, P < 0.001), and women had statistically higher mean LCM concentration than did men, 37.2 +/- 23.6 versus 26.8 +/- 12.9 mmol/L (P = 0.001). Serum LCM concentrations were significantly lower (P = 0.002) in the enzyme-inducing AED group (carbamazepine and phenytoin) compared with the LCM monotherapy group and the nonenzyme-inducing group, 23.5 +/- 11.0, 34.5 +/- 7.7, and 32.7 +/- 17.9 mmol/L, respectively. Conclusions: Serum LCM concentrations increased dose dependently, were age independent, and were higher in women compared with men. Carbamazepine and phenytoin can significantly decrease serum LCM concentrations, probably via induction of LCM metabolism.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据