SEIN - Stichting Epilepsie Instellingen Nederland, Zwolle, Netherlands; Department of Medical Genetics, University Medical Centre Utrecht, Utrecht, Netherlands.
Epilepsy Behav. 2013 Oct;29(1):217-21. doi: 10.1016/j.yebeh.2013.07.016. Epub 2013 Aug 29.
Age as well as estrogen levels may have an impact on the pharmacokinetics of lamotrigine (LTG) and monohydroxycarbazepine (MHD), the active metabolite of oxcarbazepine (OXC). To assess the effects of age and menopause, we evaluated retrospectively a therapeutic drug-monitoring database. Samples from 507 women and 302 men taking LTG and 464 women and 319 men taking OXC were used to develop a population pharmacokinetic model. Data were analyzed using NONMEM software and were compared with a population pharmacokinetic model based on samples of 1705 women and 1771 men taking carbamazepine (CBZ). Age was a significant factor contributing to pharmacokinetic variability in individuals using LTG, OXC, and CBZ with increasing clearance as a function of bioavailability (Cl/F) over age 18, a maximum Cl/F at 33years (CBZ) and 36 years (LTG and OXC), and a gradual decrease of Cl/F towards older age. We found no effect of perimenopausal age range on LTG and MHD clearance.
年龄以及雌激素水平可能会对拉莫三嗪（LTG）和单羟基卡马西平（MHD）的药代动力学产生影响，后者是奥卡西平（OXC）的活性代谢物。为了评估年龄和更年期的影响，我们回顾性地评估了一个治疗药物监测数据库。使用来自 507 名女性和 302 名男性服用 LTG 以及 464 名女性和 319 名男性服用 OXC 的样本开发了群体药代动力学模型。使用 NONMEM 软件分析数据，并与基于 1705 名女性和 1771 名男性服用卡马西平（CBZ）的样本的群体药代动力学模型进行了比较。年龄是影响使用 LTG、OXC 和 CBZ 的个体药代动力学变异性的重要因素，表现为随着年龄的增长，清除率（CL/F）呈递增函数，生物利用度（CL/F）在 18 岁以上增加，在 33 岁（CBZ）和 36 岁（LTG 和 OXC）达到最大 CL/F，随后逐渐降低。我们没有发现围绝经期年龄范围对 LTG 和 MHD 清除率有影响。
