Effect of Ethnicity on the Pharmacokinetics of 10 Antiepileptic Drugs
Abstract number :
3.250
Submission category :
7. Antiepileptic Drugs / 7F. Other
Year :
2016
Submission ID :
195815
Source :
www.aesnet.org
Presentation date :
12/5/2016 12:00:00 AM
Published date :
Nov 21, 2016, 18:00 PM
Authors :
Qianyu Wang, Yale School of Medicine; Kenneth Kato, Columbia University Medical Center; Rebecca Wong, Yale School of Medicine; Alfred Jiang, Yale School of Medicine; Richard Buchsbaum, Columbia University Medical Center; Hyunmi Choi, Columbia University M
Rationale: To date, limited data have been reported on the possible difference in antiepileptic drug (AED) clearance among ethnicities. Methods: Using the Yale-Columbia Antiepileptic Drug Database, pharmacokinetics of the 10 most commonly used AEDs was retrospectively studied in patients aged 18-65 who had been seen at either center during a 6-year period. The weight-adjusted hourly apparent clearance (CL) was calculated for each regimen and averaged for each patient using serum levels which were intended to represent steady-state trough serum concentrations. For each AED, the mean CL of each ethnic group was compared using one-way analysis of variance. Monotherapy and adjunctive therapy regimens were analyzed separately. Age, gender, and concurrent use of enzyme inducing AEDs (EIAEDs) were controlled as variables that could affect the CL of AEDs. Results: Monotherapy: The only AED used in monotherapy which exhibited a significant difference in mean CL between patients of different ethnicities was lamotrigine (LTG) (p=0.029; n=282). Mean LTG CL differed significantly between Black (25.6 ml/h/kg; n=15) and white (41.5 ml/h/kg; n=219) patients (p=0.019) as well as between Black and Hispanic (42.6 ml/h/kg; n=33) patients (p=0.039). Stepwise linear regression identified old age, male gender, and black race as significant predictors of decreased LTG CL. Polytherapy: For AEDs used in polytherapy, LTG (p=0.001; n=509) and phenytoin (PHT) (p < 0.0005; n=127) exhibited significant differences in mean CL between patients of different ethnicities. Mean LTG CL differed significantly between Black (26.9 ml/h/kg; n=36) and white (43.8 ml/h/kg; n=394) patients (p=0.001). We separately analyzed the following subgroups of patients: those taking EIAEDs, valproic acid (VPA) - a common enzyme inhibitor, a mixture of both EIAEDs and VPA, and neither an EIAED nor VPA. Although in all subgroups, a trend for decreased clearance of LTG in black patients was observed, this difference was only significant for patients who were neither on an EIAED nor an inhibitor: Black (27.1 ml/h/kg; n=23) compared to white (43.4 ml/h/kg; n=262; p=0.006). Stepwise linear regression identified male gender and black race as significant predictors of decreased LTG CL. Mean PHT CL differed significantly between Black (25.7 ml/h/kg; n=11) and white (15.2 ml/h/kg; n=98) patients (p=0.001) as well as between Hispanic (21.8 ml/h/kg; n=18) and white patients (p=0.012). Age, gender, and comedication with EIAEDs were not significantly associated with average CL. Conclusions: Black patients taking LTG as monotherapy have an approximate 40% decrease in average CL compared to white and Hispanic patients. A similar decrease is seen in Black patients taking LTG as adjunctive therapy in comparison to white patients. Meanwhile, Black and Hispanic patients taking PHT as polytherapy exhibit higher average CL compared to whites. Funding: Eisai Pharmaceuticals, Sunovion Pharmaceuticals
Antiepileptic Drugs