Therapeutic drug monitoring · 2014
Lacosamide serum concentrations in adult patients with epilepsy: the influence of gender, age, dose, and concomitant antiepileptic drugs.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Markoula Sofia, Teotonio Rute, Ratnaraj Neville, Duncan John S, Sander Josemir W, Patsalos Philip N
Аннотация
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 μmol/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 μmol/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.
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 μmol/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 μmol/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.