title: The impact of age on lamotrigine and oxcarbazepine kinetics: a historical cohort study.
abstract: 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.
authors.affiliation: SEIN - Stichting Epilepsie Instellingen Nederland, Zwolle, Netherlands; Department of Medical Genetics, University Medical Centre Utrecht, Utrecht, Netherlands. Electronic address: iwegner@sein.nl.
authors.forename: Ilse
authors.initials: I
authors.lastname: Wegner
authors.forename: Abraham J
authors.initials: AJ
authors.lastname: Wilhelm
authors.forename: Josemir W
authors.initials: JW
authors.lastname: Sander
authors.forename: Dick
authors.initials: D
authors.lastname: Lindhout
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000187:drug effects*; D000927:Anticonvulsants / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D000078330:Oxcarbazepine; D014227:Triazines / Q000493:pharmacokinetics* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D014227:Triazines; D002220:Carbamazepine; D000077213:Lamotrigine; D000078330:Oxcarbazepine
keywords: Age; Carbamazepine; Epilepsy; Lamotrigine; Menopause; Oxcarbazepine; Pharmacokinetics; Therapeutic drug monitoring