Within-Subject Variability of Lamotrigine Bioavailability: Analysis of Equigen Study Data
Abstract number :
1.330
Submission category :
7. Antiepileptic Drugs / 7E. Other
Year :
2018
Submission ID :
497463
Source :
www.aesnet.org
Presentation date :
12/1/2018 6:00:00 PM
Published date :
Nov 5, 2018, 18:00 PM
Authors :
Alyssa Sykuta, Drake University; Lendie Follett, Drake University; Timothy Welty, Drake University; Marcia Laugerman, Drake University; Barry E. Gidal, University of Wisconsin School of Pharmacy; Michael Privitera, University of Cincinnati Medical Center;
Rationale: Lamotrigine (LTG) is a common drug in the treatment of epilepsy. Multiple pharmacokinetic studies have evaluated LTG, but few studies on within-subject variability (WSV) are available. Wide WSV is an important factor in treatment success for many medications used in other diseases (e.g., HIV, transplantation). Understanding factors associated with wide WSV is important in clinical practice, bioequivalence studies, and clinical trials. The objective of this study was to determine factors associated with wide WSV of LTG in the Equigen study. Methods: Data from the EQUIGEN chronic dose (n=35) and single dose (n=50) generic substitution trials were analyzed to determine WSV for AUC, and for Cmax. We calculated: 1) percent difference from time t to time t+1; 2) percent difference between the maximum and minimum values; 3) whether the differences were >20% WSV. Factors in the analysis were age, sex, weight, smoking, coffee, and PK visit number, which were analyzed to determine their relationship to the calculated WSV. Results: In the EQUIGEN chronic dose study, females showed significantly higher variability in AUC0 to time t compared to males (p=0.02). Findings for all other variables also consistently suggested females displayed wide WSV for LTG compared to males. Additionally, the WSV of Cmax was noted to increase as subjects progressed through the study sequences(p=0.006). For the EQUIGEN single-dose study, increased weight was found to be associated with lower WSV across all variables (p=0.02). Conclusions: These findings suggest that sex may be related to wide WSV for LTG in chronic-dose patients. Single-dose patients with higher BMI may experience lower WSV with LTG. The findings of this study suggest possible factors leading to wide WSV for LTG. Clinically, there may be greater fluctuations with lamotrigine concentrations in women. Further study into these factors and their implications for clinical practice, bioequivalence studies, and clinical trials is needed. Funding: Funded by a Prime grant to FEFA, LLC is from Funding Entity: U.S. Department of Health and Human Services/Food and Drug Administration/Office of Acquisitions and Grants Services/Division of Contracts and Grants Management (DHHS/FDA/OAGS/DCGM).